The role of Annie was originally offered to Julia Roberts, who turned it down.
Kim Basinger was also offered the role of Annie in the early script process, but turned it down because she thought the premise was ridiculous. Dennis Quaid was also considered for the male lead.
A pre-"Seinfeld" reference to the real-life "Soup Nazi": A male journalist is speaking as Meg Ryan enters an office at her newspaper, saying, "...he's the meanest guy in the world, but he makes the best soup you've ever eaten."
Mary Kelly was the name Sam Baldwin gave as the eighth girl he "made it with" in college. Mary A. Kelly is the Script Supervisor and also played a bit role as the nervous woman on the plane.
Meg Ryan and Tom Hanks only share approximately two minutes screen time together.
The airplane scenes are actually shot at the Boeing plant in Renton, Washington - inside the actual sales mock-ups.
When Meg Ryan's character is in the kitchen in the middle of the night listening to the 'best of' radio callers, the caller 'Disappointed in Denver' is voiced by director Nora Ephron.
The silhouette of the couple on the box of chocolates in a shop window outside Annie's house is, in fact, a silhouette of Tom Hanks and Meg Ryan.
[June 2008] Ranked #10 on the American Film Institute's list of the 10 greatest films in the genre "Romantic Comedy".