A nurse by training, Annie is a devoted fan of the works of romance author Paul Sheldon, whom she rescues after a car accident and brings back to her home.

A heavily altered version of the character also acts as main protagonist of the second season of the television series Castle Rock (itself loosely based on various works of King) in 2019, in which she is primarily portrayed by Lizzy Caplan.

In both the book and film, Wilkes rescues protagonist Paul Sheldon after he breaks both of his legs in a car accident, and takes him to her home to convalesce.

She fawns over Sheldon, a writer of romance novels starring her favorite literary character, Misery Chastain; she professes to be his "number one fan" and says that she loves him.

On one of his trips out of his room, Sheldon finds Wilkes' old scrapbook and learns from the newspaper clippings inside that she is a serial killer whose spree dates back to her childhood in Bakersfield.

Sheldon also learns that she killed several patients at other hospitals where she worked, but no one suspected foul play because the victims were either elderly or gravely injured.

Sheldon also finds that Wilkes was formerly married to a physical therapist named Ralph Dugan, who later divorced her, citing "mental cruelty".

In the book, she chops off his foot with an axe and cauterizes it with a blowtorch and later cuts off one of his thumbs with an electric knife when he complains about a missing letter on his typewriter (neither of these things happen in the film).

In the book, Wilkes murders a Colorado state trooper who sees Sheldon in her house by stabbing him with a wooden cross and running him over with a lawnmower.

For instance, when Sheldon complains that the packet of Eaton's Corrasable Bond paper she bought for him is smudge-prone, she smashes his still-healing knee; in the book, when he mentions that her typewriter is missing a key, she cuts off his thumb.

King has noted that Wilkes "may seem psychopathic to us, but it's important to remember that she seems perfectly sane and reasonable to herself – heroic, in fact, a beleaguered woman trying to survive in a hostile world filled with cockadoodie brats".

[3] In a special feature on the collectors' edition DVD, forensic psychologist Reid Meloy said that Wilkes' personality (as portrayed by Kathy Bates) is a virtual catalog of mental illness.

[4] In his commentary on the film available on the DVD, director Rob Reiner notes that Wilkes is loosely based on Genene Jones, a nurse who is believed to have killed as many as 50 children who were in her care over a two-year period.

In the novel, which is set in Newman's alternate history crossover Anno Dracula series, Wilkes is the murderer of John Lennon.

Kathy Bates reprised her role as Annie Wilkes in a 2008 commercial for DirecTV, with the setting being the infamous scene where she breaks Paul Sheldon's ankles.