Judd Apatow and Adam Sandler were old roommates. The footage seen in the opening sequence was recorded back then. Sandler would regularly make prank phone calls and one day Apatow decided to start filming them.
When Ira is playing the mix he made for George, George objects to the first song because Bob Marley died of cancer, which reminds George of his own medical condition. Actually, all three of the songs that Ira plays have a strong connection to a famous man who died of cancer: in addition to the Bob Marley song, he plays "(I've Had) The Time of My Life", which is most famous for its prominent inclusion in the movie Dirty Dancing (1987) (that movie's star, Patrick Swayze, was undergoing treatment for pancreatic cancer while this movie was being filmed, and he died in September 2009), and next, he plays "Keep Me In Your Heart" by Warren Zevon, who died of lung cancer in 2003.
The film's soundtrack features songs from each of The Beatles' solo careers. Adam Sandler performs a cover of John Lennon's song "Real Love" at about the halfway point of the movie during his paid jam session.
Aziz Ansari's character, Randy, proved to be so popular on the set with the cast and crew that Judd Apatow shot a Randy "documentary" and is developing a Randy feature film. Ansari also incorporated Randy into his regular stand-up act. Ansari has said that he based Randy on Soulja Boy. He imagined what if Soulja Boy was a stand-up comedian and wrote jokes based on that idea.
In the film, Eric Bana jokes about how Cameron Diaz is hotter than Leslie Mann's character - Leslie Mann would go on to co-star with Cameron Diaz in The Other Woman where her husband cheated with Cameron Diaz.
When Seth Rogen's character talks about his camp experience at a camp called "Mahaneh Miriam", this is a reference (by its Hebrew name) to the camp that Rogen went to growing up. This camp is a Jewish camp located in British Columbia affiliated to the youth movement Habonim Dror.
The scene in which Ira (Seth Rogen) is waiting for George to pick him up for the MySpace gig, he is talking to Leo and Mark on the balcony. During the shot of Ira speaking you can see a Green Hornet poster on the dresser in the back. Seth Rogen starred in the remake of The Green Hornet (2011).
In Knocked Up (2007), there is a scene where the guys are sitting around talking about that, if they "got laid", it was because of Eric Bana in Munich (2005). Bana also stars in this film, and coincidentally (or perhaps not) the director of photography on both Munich (2005) and this film is Janusz Kaminski. Barry Mendel, one of the producers of Munich (2005), is also a producer on this film as well.
The film features Warren Zevon songs "Keep Me in Your Heart" and "Numb as a Statue" from the 2003 Album "The Wind". Zevon began recording the album shortly after he was diagnosed with inoperable lung cancer and it was released just two weeks before his death.
RZA appears in this film. The opening scene of Knocked Up (2007), Judd Apatow's previous directorial film, is set to the song "Shimmy Shimmy Ya" by 'Ol Dirty Bastard', which was co-written and produced by the RZA.
Eric Bana's character is, like Bana himself, a St Kilda supporter, which is a team in the Australian Football League (AFL). Bana attended the 2009 AFL Grand Final in which St Kilda was playing. (They unfortunately lost by 12 points to Geelong.) In 2010, St Kilda again made the Grand Final, this time against Collingwood - the very same opponents that Bana's character despises. A rare replay was scheduled for Saturday 2 October 2010 after the first Grand Final ended in a draw at 68 points each.
The trivia items below may give away important plot points.
Adam Sandler said, in interviews shown in the credits of Australian pay TV viewings, that casting Eric Bana made the fight sequence more realistic, especially because the Australian would be seen as the stronger combatant.