Sofia Vassilieva shaved her hair and eyebrows off in order to play Kate Fitzgerald. She described it as being the least she could do to understand Kate's pain. Because she was filming both this movie and the TV show Medium (2005), her hair on the show was a wig.

Real-life sisters Elle Fanning and Dakota Fanning were originally set to play Anna and Kate Fitzgerald, but bowed out after Dakota Fanning reportedly refused to shave her head, as required for the part.

Although Cameron Diaz's character in the movie shaves her head, Diaz did not actually do so in real life. Sophia Vassilieva, who played Diaz's cancer-striken daughter, did, however, shave her head in both the movie and in real life.

Evan Ellingson lost his own brother (to a drug overdose) when he was making the film.

Cameron Diaz's father died of pneumonia during production. He was only 58.

This is the first time Cameron Diaz has played a mother. Diaz has no children in real life.

Producer Scott Goldman optioned the rights to Jodi Picoult's book before it was even published.

Cameron Diaz wore a bald cap instead of shaving off her own hair. This was more for practical reasons as Diaz only needed to be bald for just two scenes.

The sixth film to be directed by Nick Cassavetes.

All of the siblings in the movie are 4 years apart from each other. Jesse 4 years older than Kate who is 4 years older than Anna

Thomas Dekker shaved his head for the film.

This movie is based on the book "My Sister's Keeper" by Jodi Picoult. However, at the end of the movie, Kate dies. In the book, Anna wins her court case, then while driving to the hospital with her attorney, they are in an accident. Anna is brain dead, and her lawyer, who now has power of attorney, gives permission for her kidney to be given to Kate. Kate then makes a full recovery and goes into remission.