The film dramatizes the efforts of former Oakland County, Michigan, pathologist Jack Kevorkian (Pacino) to help the terminally ill and the profoundly disabled end their lives.

He is assisted by his sister Margo Janus (Vaccaro), as well as his longtime friend and medical technician Neal Nicol (Goodman), and Janet Good (Sarandon), who founded the eastern Michigan chapter of the Hemlock Society.

Kevorkian is unsuccessfully tried four times, but after taking an unprecedented direct role in the August 1998 death of his final patient Thomas Youk, he is convicted of second degree murder and is sentenced to 10-to-25 years in prison.

You Don't Know Jack's screenplay is largely based on the book Between the Dying and the Dead by Neal Nicol and Harry Wylie.

Al Pacino won Primetime Emmy, Golden Globe and Screen Actors Guild awards for his performance as Kevorkian.

In an interview with reporter Jack Lessenberry, Kevorkian denounces what he sees as the cruelty of his unnecessarily painful death, comparing it to the Holocaust.

Youk, reputed to be Kevorkian's final patient, is so crippled by amyotrophic lateral sclerosis (ALS) that he cannot self-administer the drugs.

A video of Youk's death is presented as part of Kevorkian's interview with reporter Mike Wallace of the CBS news program 60 Minutes.