Conceived by means of in vitro fertilization, Anna Fitzgerald (Abigail Breslin) was brought into the world to be a genetic match for her older sister, Kate (Sofia Vassilieva), who suffers from acute promyelocytic leukemia, in order to keep her alive. Her family members are introduced one by one and each tell about how Kate's illness has affected them personally and the family. When Kate turns 15, she goes into renal failure. Anna knows that she will be forced by her parents to donate a kidney. She also believes that, if she does donate a kidney, she will be unable to live the life she wants. She erroneously fears that she will not be able to cheer-lead, play soccer, or be a mother. Anna tells her parents that she does not want any of this, and proceeds to sue them for medical emancipation and the rights to her own body. Her overprotective mother, Sara (Cameron Diaz) is indignant at Anna's decision and even strikes her across the face when she receives the notice of intended prosecution. Attorney Campbell Alexander (Alec Baldwin) agrees to work for Anna as her guardian ad litem, suing for partial termination of parental rights. It is later learned he agreed to take the case not for the notoriety, but because he has epilepsy and understands her predicament of not having control over one's own body.
The film is interlaced with flashbacks that detail Kate and Anna's closeness, as well as how Kate's illness has affected her siblings' lives and their relationships. In a flashback, Kate also meets a fellow cancer patient, Taylor Ambrose (Thomas Dekker), whom she begins dating. After a date, they share their first kiss outside Kate's house, with Sara and Brian watching from their bedroom window. After this, he becomes her boyfriend in and out of hospital and supports her as she undergoes treatment. He then asks her to the hospital's "prom" for patients-- there, they slow-dance, then proceed to a vacant hospital room to have intercourse. A few days later, Kate is crying because Taylor hasn't called her for several days. Her mother Sara is furious when Kate mentions they did "stuff" after the prom and storms out to ask the nurse where Taylor is, evidently believing that he had dated her daughter purely for his own ends, and learns that he has passed away.
To Sara's dismay, the judge (Joan Cusack), Judge de Salvo, refuses to grant summary dismissal, and the case goes to a hearing. During the hearing, Anna and Kate's older brother, Jesse, unable to get Anna to admit it, reveals that Anna is actually acting under Kate's instruction; Kate has no confidence in another operation and would rather be allowed to die peacefully, and since Sara refuses to budge in her desire to keep her alive, she had secretly urged Anna to file for medical emancipation, and refuse to donate a kidney. At around the same time, Kate makes a request to go to the beach one last time, and Brian, her father, obtains permission from her doctor and removes her from the hospital to take her and the kids. Overprotective as ever, Sara is furious when Brian shows up at the house with Kate and demands her to be returned to the hospital. Brian angrily refuses and drives off, threatening Sara with a divorce if she does not join them. Sara later shows up at the beach, where they enjoy one final family outing. Before the case is settled, Kate dies in her sleep at the hospital with her mother by her side. After Kate's death, Campbell brings the court decision – Anna won the case. The family moves on with their lives, being changed by Kate's death, but every year on Kate's birthday they go to Montana, which was her "most favorite place in the world." Anna also wonders why Kate had to die but she got to live. At the end, Anna says that their relationship continues because she will see Kate again.
***
Anna Fitzgerald's older sister, Kate, suffers from acute promyelocytic leukemia, a cancer of the blood and bone marrow. Anna was conceived in order to harvest blood from her umbilical cord in order to use in treatments to help save Kate's life; although the treatment was initially successful, Kate relapsed; ever since, Anna - the only compatible family member, since both her parents and her older brother Jesse are incompatible donors - has been used as a donor for any other bodily substance needed to treat Kate, who continues to swing between remission and relapse as she grows up.
Anna is usually willing to donate whatever Kate needs, but when she is thirteen, she is told that she will have to donate one of her kidneys. The surgery required for both Kate and Anna would be major; it is not guaranteed to work, as the stress of the operation may well kill Kate anyway; and the loss of a kidney could have a serious impact on Anna's life. Anna petitions for medical emancipation with the help of lawyer Campbell Alexander, so that she will be able to make her own decisions regarding her medical treatment and the donation of her kidney.
Anna's mother, Sara, is an ex-lawyer and decides to represent herself and her husband in the lawsuit. Over the course of the novel, she tries on several occasions to make Anna drop the lawsuit. Anna refuses to do so, but the resulting tension between her and her mother result in her moving out of the house to live with her father Brian in the fire station where he works. This is done on the advice of Julia Romano, the court-appointed guardian ad litem whose job it is to decide what would be best for Anna. Julia was once romantically involved with Campbell when they went to school together, but Campbell broke her heart when he left her.
Meanwhile, Jesse - who has spent most of his life being ignored in favor of ill Kate or organ donor Anna - spends most of his time setting fire to abandoned buildings with home-made explosives, using the knowledge that his fire-fighter father gave him to make the fires bigger and fiercer, and doing drugs. He is a self-confessed juvenile delinquent and pyromaniac, and the only time throughout the book that his parents pay him any attention is when Brian discovers that it has been him who was setting the fires. Brian forgives him, and by the end of the book, he has reformed and graduated from the police academy.
During the trial, it is revealed that Kate asked Anna to sue for emancipation because she did not want Anna to have to transplant, and because she believes that she will die anyway. The judge rules in Anna's favor, and grants Campbell medical power of attorney. However, as Campbell drives her home after the trial their car is hit by an oncoming truck. Brian retrieves Anna, who is unconscious, and suffers an injury to the head, and Campbell, who suffers an injury to the arm, from the wreckage of the crushed car and rushes them to hospital. However, after some time, the doctor informs them that Anna is brain-dead, that the machines keeping her alive may as well be switched off, and asks them if they have considered organ donation. Campbell steps in, and declares that he has the power of attorney, and "there is a girl upstairs who needs that kidney". Kate is prepped for surgery, and Anna's kidney is successfully transplanted. Kate survives the surgery and goes into remission. Most of Anna's usable organs are removed for transplants in the future. Kate stays in remission for at least 6 years, while Anna dies for her sister's life.