- Dawson Casting: Inverted. Abigail Breslin was two years younger than her character in the book. Evan Ellingson was twenty playing a teenage Jesse. Sofia Vassilieva was the same age as her character, however.
- Dyeing for Your Art: Sofia Vassilieva shaved her head for the role. She was still filming Medium at the time, so her own hair was turned into a wig for it. Averted with Sara's head-shaving scene as Cameron Diaz just wore a bald cap. This was for practical reasons, as Diaz only had to be bald for two scenes as opposed to the entire film. Thomas Dekker also shaved his head to play Taylor.
- Life Imitates Art: Evan Ellingson (Jesse) lost his own brother while filming the movie.
- Playing Against Type: Cameron Diaz, usually known for rom-coms and playing ditzy characters, plays My Beloved Smother towards a cancer patient.
- Star-Making Role: This film, coupled with the show Medium, snowballed Sofia Vassilieva's acting profile.
- What Could Have Been: Originally, Anna and Kate were supposed to be played by Dakota and Elle Fanning, but the former backed out when she found out that her head was to be shaved for the part, leaving the latter to back out as well. Ironically, Dakota went on to play a cancer-stricken girl in the film Now Is Good.
Trivia / My Sister's Keeper