The original title for the script was 'Fuck Buddies' but this wouldn't make it past the MPAA. It was changed to "Friends With Benefits", but then that title was changed because there was another movie with the same title, Friends with Benefits (2011), starring Mila Kunis and Justin Timberlake. By the time pre-screening invitations were made, it had still not been decided whether the title would be No Strings Attached (2011) or Hooking Up.
Natalie Portman originally entered the project as a producer and not as a member of the cast. She remained an executive producer after being cast as Emma. The film is credited as a production of Portman's production company, Handsomecharlie Films.
The song performed by Adam's dad for his birthday was actually written and composed by Kevin Kline, who plays the character.
This movie is known to be very similar to Friends with Benefits (2011) which stars Ashton Kutcher's then real life partner, Mila Kunis.
During Adam's birthday scene as he was blowing out candles, there is a Creation of Adam painting on the cake. That was Kevin Kline's idea to add it onto the cake.