John Quincy Archibald's son Michael collapses while playing baseball as a result of heart failure. John rushes Michael to a hospital emergency room where he is informed that Michael's only hope is a transplant. Unfortunately, John's insurance won't cover his son's transplant. Out of options, John Q. takes the emergency room staff and patients hostage until hospital doctors agree to do the transplant.

In Los Angeles, the eleven year old Anna Fitzgerald seeks the successful lawyer Campbell Alexander trying to hire him to earn medical emancipation from her mother Sara that wants Anna to donate her kidney to her sister. She tells the lawyer the story of her family after the discovery that her older sister Kate has had leukemia; how she was conceived by in vitro fertilization to become a donor; and the medical procedures she has been submitted since she was five years old to donate to her sister. Campbell accepts to work pro bono and the obsessed Sara decides to go to court to force Anna to help her sister.

Jake is killed by neighbourhood thugs, and returns as a mystical figure (The Wraith) to gain revenge.

In the mid-1990s, two inmates bury the burned bodies of two lifers at Mississippi's infamous Parchman Farm; a third old-timer relates their story. They'd served 65 years for a murder they didn't commit, framed by a local sheriff while buying moonshine whiskey for a Manhattan club owner to whom they owed money. In flashbacks we see this odd couple thrown together (Ray is a fast-talking con man, and Claude is a serious man about to start work as a bank teller), the loss of Ray's watch (sterling silver, from his daddy), the murder and trial, the hardships of Parchman, and the love-hate relationship of Claude and Ray as they spend 65 years bickering and looking for a way to escape.