Cross the Streams (also known as Crossing the Streams) is in reference to when two or more Proton Streams cross paths.
It was spoken of twice by Egon Spengler, (and performed once,) in 1984. During the Ghostbusters' first case, in the Sedgewick Hotel, Egon warns everyone to never "Cross the Streams", which refers to the proton beams from multiple Particle Throwers crossing paths during use. Egon noted "It would be bad." Peter Venkman countered he was fuzzy on the whole good/bad thing and asked him what he meant by "bad." Egon clarified with an example. He told them to try to imagine all life as you know it stopping instantaneously and every molecule in your body exploding at the speed of light. Ray Stantz realized he was talking about total protonic reversal.
Several weeks later, to defeat Gozer, Egon told everyone to cross the streams, knowing full well the risks. He informed them there was definitely a very slim chance they would survive. They reversed the flow, banished Gozer, Zuul, and Vinz Clortho, and blew up the Stay Puft Marshmallow Man, the Temple of Gozer, and 550 Central Park West. Seven years later, on the Thanksgiving 1991 holiday, the Ghostbusters crossed the streams to destroy Ivo Shandor.
The Real Ghostbusters
During the Captain Steel and Dr. Destructo incident, the Ghostbusters were mistaken as supervillains by Steel. Captain disarmed them with his heat vision and bent a steel pole around all of them. Captain picked them up and flew off with them in hand but Dr. Destructo blasted Steel making him drop the Ghostbusters. In order to save themselves from falling to their death, the Ghostbusters pointed their Particle Throwers at the water below and crossed the streams.  This created a large plume of water that cushioned their impact. Egon Spengler later admitted he didn't know it would have saved their lives or not.
Abby Yates prioritized the need to reverse the Portal but it required an insane amount of energy. Erin Gilbert wondered what to do. Abby believed they just had to shoot directly in the portal with more power to cause a reverse reaction. Jillian Holtzmann suggested they cross the streams. Erin remembered that was the thing that was so powerful that would make all of their atoms implode. Holtzmann corrected her and thought it would be more violent than that. Abby believed they had an extremely good shot at pulling all the ionized ecto-matter back into the dimension of its origin by crossing their streams into the portal. Erin saw the pro was they saved the world but the con was they experienced the most painful death conceivable of all time. Abby admitted it was hard to shine that penny. Erin agreed to do it. They returned to the portal and crossed the streams into it. The Ghostbusters fell on their backs from the recoil. Abby realized it wasn't enough power to alter the polarity. They blew up the silver reactors atop Ecto- instead and successfully changed the portal's polarity then it forcefully pulled all the ghosts back in it.
In theory, crossing the streams on the Temple of Gozer's doorway took the Ghostbusters right up to the line of complete subatomic destruction. For a split second, they were connected to every reality at once via Gozer's portal. Every thought they ever had, the very core of their beings, were seeded into the subconscious of the Multiverse. The concepts and methods of the Ghostbusters were adopted by parallel versions of the team.  During one spring season, nine Ghostbusters crossed the streams on Tiamat in a battle atop Dana's current apartment. They were returned to the physical plane and both Dana Barrett and Louis Tully were restored to normal but Tiamat's presence was still felt when Blood Rain showered on them and a disembodied laugh could be heard.
During the finale of the dimensional bleed incident, the two teams of Ghostbusters successfully captured the Bronx Spook but the breach left behind did not close. Erin Gilbert realized they needed a catalyst to close the breach and start the reaction that would work on the molecular level to separate the two dimensions. She suggested crossing the streams. Ray objected and called it a terrible idea. Peter was more open to it since they survived the last few times. Egon agreed with Ray but knew there was no other choice. After they crossed the streams, Jillian Holtzmann admitted she was panicking and observed it felt like being pulled in a million directions at once. The atoms of both worlds began to scatter, mingle, and separate as they came very close to the verge of protonic reversal. For seconds, the universes were joined and everything they experienced became one timeline then the fabric of reality was shaken enough and the two dimensions were restored to normal. Egon hypothesized there may be some residual memories from the atomic co-mingling. Rebecca Gorin likened it to a living representation of Escher's Relativity.
- In the August 5, 1983 draft of the first movie, Egon tells everyone to go full stream with strogon pulse then cross their streams onto the Stay Puft Marshmallow Man but it fails. Like in the movie, he is only ignited and angered.
- In Ghostbusters: The Video Game, in the realistic versions, if the player crosses the streams with a teammate for too long, then the streams will overload, sending a pulse back along the stream and knocking both characters down.
- The explosion that results in crossing streams during gamepley in the video game appears to be much less harmful than the result as seen in the movie. This is due to a fail safe mechanism in the experimental Proton Pack named the "cross-stream governor." At the end of the game, Egon tells everyone he's deactivating them on all the packs then they cross the streams to destroy Ivo Shandor.
- In the realistic version, after Museum of (Super)Natural History, the seventh message on the Firehouse answering machine inquires about crossing the streams in a humorous manner. 
- On page 19 of Ghostbusters Volume 1 Issue #3, Peter Venkman suggests they use the cross the streams strategy to save the day. 
- On page 18 of Ghostbusters Volume 1 Issue #15, Winston Zeddemore suggests crossing the streams on the Megaspook but Egon shoots down the idea on the notion there is no extradimensional portal to skew the results. 
- On page 19 of Ghostbusters Volume 2 Issue #20, Peter alludes to Crossing the Streams. 
- On page 3 of Teenage Mutant Ninja Turtles Ghostbusters Issue #3, Ray mentions to not cross the streams. 
- On page 11 of Teenage Mutant Ninja Turtles/Ghostbusters Issue #4, Winston mentions crossing the streams. 
- The subject of Ghostbusters: Deviations revolves around what if the Ghostbusters never crossed the streams on the Temple of Gozer because of the inherent catastrophic danger in doing so. Gozer even suggests they do it so he can return to his home dimension but they still refuse and cite the whole planet could be destroyed.
- On page 18 of Ghostbusters 101 #3, Jillian Holtzmann alludes to the urinating joke that came from the crossing the streams term in the first movie.
- On page 11 of Transformers/Ghostbusters Issue #3, Egon replies "That would be bad," similar to when he informed the team about crossing the streams in the first movie.
- On page 13 of Ghostbusters Year One Issue #4, Egon reveals shooting the Proton Grenade would be effectively crossing the streams.
- Ghostbusters: The Video Game (Realistic Versions)
- The Real Ghostbusters
- Extreme Ghostbusters
- IDW Comics
- Ongoing Series
- Volume 2
- Ghostbusters 101
- Ghostbusters Crossing Over
- Ghostbusters IDW 20/20
- Ghostbusters Year One
- Ongoing Series
- Insight Editions
- Ghostbusters (2016 Movie)
- Ghosts From Our Past: Both Literally & Figuratively: The Study of the Paranormal
- Mentioned on Page 137.
- Egon Spengler (2009). The Real Ghostbusters - "Captain Steel Saves the Day" (1987) (DVD ts. 11:33-11:35). Time Life Entertainment. Egon says: "Aim at the water and cross the streams!"
- Jillian Holtzmann (2016). Ghostbusters (2016 Movie) Extended Edition; Chapter 15 (2016) (Blu-Ray ts. 1:52:55-1:52:56). Sony Pictures. Jillian Holtzmann says: "We gotta cross the streams."
- Jillian Holtzmann (2016). Ghostbusters (2016 Movie) Extended Edition; Chapter 15 (2016) (Blu-Ray ts. 1:53:01-1:53:03). Sony Pictures. Jillian Holtzmann says: "No, implode is the wrong word. It'll be more violent than that."
- Abby Yates (2016). Ghostbusters (2016 Movie) Extended Edition; Chapter 15 (2016) (Blu-Ray ts. 1:53:03-1:53:09). Sony Pictures. Abby Yates says: "We gotta cross 'em up, and we've got an extremely good shot at pulling all the ionized ecto-matter back into the dimension of its origin."
- Erin Gilbert (2016). Ghostbusters (2016 Movie) Extended Edition; Chapter 15 (2016) (Blu-Ray ts. 1:53:12-1:53:16). Sony Pictures. Erin Gilbert says: "And on the negative side, we experience the most painful death conceivable of all time."
- Abby Yates (2016). Ghostbusters (2016 Movie) Extended Edition; Chapter 15 (2016) (Blu-Ray ts. 1:54:06-1:54:09). Sony Pictures. Abby Yates says: "The portal's too strong. We still don't have enough power to reverse it."
- Egon Spengler (2017). IDW Comics- "Ghostbusters 101 #3" (2017) (Comic p.18). Egon Spengler says: "It took us right up to the line of a complete subatomic destruction. And by way of Gozer's portal, for a split second, we were connected to every reality at once. Every thought we ever had, the very core of our beings... that's how they were seeded into the subconscious of the Multiverse. Our concepts, our methods... In theory, anyway. But so far, observation has only lent the idea credibility."
- Aykroyd, Dan & Ramis, Harold (1983). Ghostbusters (First Draft August 5, 1983) (Script p. 129). Egon Spengler says: "Full-stream with strogon pulse. We'll cross the beams."
- Egon Spengler (2009). Ghostbusters: The Video Game (Realistic Version)- Central Park Cemetery Level "In cinematic after final boss battle" (2009) (PC/PS3/Xbox 360). Atari. Egon Spengler says: "I'm deactivating the cross-stream governor!"
- Male Caller; After Museum of (Super)Natural History, Firehouse 2nd Floor Answering Machine Message 7 of 11 (2009). Ghostbusters: The Video Game (Realistic Versions) - Firehouse (2009) (PC/PS3/Xbox 360). Terminal Reality. Male says: "I was just calling because I was really confused about something. Me and my buddies have been going fly fishing for years and never once had any trouble crossing the streams."
- Peter Venkman (2011). IDW Comics- "Ghostbusters Volume 1 Issue #3" (2011) (Comic p.19). Peter says: "We'll lickety-split it on over to his usual haunt, cross some streams, and be back in time for the news."
- Winston Zeddemore (2012). IDW Comics- "Ghostbusters Volume 1 Issue #15" (2012) (Comic p.18). Winston says: "Should we Cross the Streams?!"
- Peter Venkman (2014). IDW Comics- "Ghostbusters Volume 2 Issue #20" (2014) (Comic p.19). Peter says: "We can't always be lucky enough to save the world with five seconds of focused zapping."
- Ray Stantz (2014). IDW Comics- "Teenage Mutant Ninja Turtles/Ghostbusters Issue #3" (2014) (Comic p.3). Ray says: "Oh yeah - be careful not to cross the streams! Protonic reversal isn't on my list of things to do today!"
- Winston Zeddemore (2015). IDW Comics- "Teenage Mutant Ninja Turtles/Ghostbusters Issue #4" (2015) (Comic p.11). Winston says: "Uh, we're wedged in pretty tight, man. I can't reach my Trap without crossing your stream."
- Ray Stantz (2009). The Real Ghostbusters - "The Boogieman Cometh" (1986) (DVD ts. 18:12-18:17). Time Life Entertainment. Ray says: "The laws of physics are different here. It could be even worse than crossing the streams!"
- Egon Spengler (2009). Extreme Ghostbusters- Darkness at Noon, Part 2 (1997) (DVD ts. 2:55-2:59). Sony Pictures Home Entertainment. Egon says: "The important thing to remember is that you must never under any circumstances, cross the streams."
- Ghostbusters 101 Class Notes (2017). IDW Comics- "Ghostbusters 101 #4" (2017) (Comic p.23). Ghostbusters 101 Class Notes reads: "All packs have one important rule: do NOT cross the streams. This can cause a chain reaction, which may lead to total protonic reversal (or destruction at the cellular level). Crossing streams is like Russian roulette, protonic reversal may never happen. But it might."
- Prime Ghostbusters Biography (2018). IDW Comics- "Ghostbusters Crossing Over Issue #3" (2018) (Comic Dramatis Personae p.1). Line reads: "The original Ghostbusters of the Prime Dimension, who defeated Gozer by crossing the streams-seeding the multiverse with their memories and methodology, and creating Ghostbusters teams across the interdimensional landscape."
- Kylie Griffin (2018). IDW Comics- "Ghostbusters Crossing Over Issue #8" (2018) (Comic p.5). Kylie Griffin says: "We didn't beat Tiamat by crossing a dozen streams - what other choice do we have?!"
- Gabriel Sitter (2019). IDW Comics- "Ghostbusters IDW 20/20" (2019) (Comic p.18). Gabriel Sitter says: "At least we're not prancing in front of a dinosaur, or crossing streams, or - oh crap."
- Egon Spengler (2020). IDW Comics- "Ghostbusters Year One Issue #4" (2020) (Comic p.13). Egon Spengler says: "The prototype carries a positive proton charge. Your stream might damage it and release the energy. You'd be effectively crossing streams."
- Narrator (2016). Insight Editions- "Tobin's Spirit Guide" (2016) (Book p.81). Paragraph reads: "Ultimately, Gozer's physical essence was destroyed when we crossed our individual proton streams (risking total protonic reversal) and aimed them at the temple from which the deity had emerged into this plane of existence."
- Jillian Holtzmann (2016). Ghostbusters (2016 Movie) Extended Edition; Chapter 9 (2016) (Blu-Ray ts. 1:02:51-1:02:54). Sony Pictures. Jillian Holtzmann says: "Erin, I forgot to tell you, don't let your beam get entangled with my beam."
- Jillian Holtzmann (2016). Ghostbusters (2016 Movie) Extended Edition; Chapter 9 (2016) (Blu-Ray ts. 1:02:56-1:03:02). Sony Pictures. Jillian Holtzmann says: "It's too much power. It would cause a counter reaction. The beam would shoot back into your body, and each atom will implode."
- Shaffer, Andrew (2016). Ghosts From Our Past: Both Literally & Figuratively: The Study of the Paranormal, p. 137. Three Rivers Press, New York NY USA, ISBN 9781101906002.Line reads: "Plasma stream convergence is highly, highly discouraged."