Pam's sister Deborah, a supporting character in Meet the Parents (2000), is mentioned in the film, but does not appear on-screen. Nicole DeHuff, the actress who played her, died in 2005.
When Robert De Niro won the Lifetime Achievement Award at the Golden Globes he remarked: "I was very, very moved and gratified when you made the announcement (of this award) two months ago, well before you had a chance to review Little Fockers."
Dustin Hoffman initially declined to reprise his role as Bernie Focker, being unhappy with the script, and the replacement of director Jay Roach with Paul Weitz, so the character was originally killed. However, both Hoffman and Universal eventually agreed on him shooting six scenes.
During a publicity junket for The Guilt Trip (2012), Barbra Streisand confessed she hadn't seen this movie from start to finish, the only one of her films that she had so neglected. She did admit that her individual scenes were sent to her via disc for approval while she was staying at a spa in Switzerland.
(at around 1h 30 mins) When Jack Byrnes watches the video on YouTube, the URL in the title bar is for the video "Robert De Niro imagines he's Elmo!"