Annie was born in Bakersfield, California and she graduated from the University of California at the Los Angeles nursing school in 1966. While serving as head maternity nurse at a Boulder, Colorado hospital, several infants in her care died under mysterious circumstances. She was tried for their deaths, but she acquitted for lack of evidence. But the press — which called her "the Dragon Lady" — strongly implied that she was in fact guilty. Paul also learns that she killed several patients at other hospitals where she worked, but no one noticed because they were either very sick or suffered debilitating injuries beforehand. Annie also killed her father, her childhood neighbors and their father, a hitchhiker she once slept with, all told almost 70 people. Paul also finds out that Annie used to be married to a physical therapist named Ralph Dugan, who later divorced her citing "mental cruelty".
She is Paul Sheldon's alleged number one fan, although she is actually a lonely psychopath who is completely obsessed wth him. Wilkes is stalking Sheldon after he leaves the Silver Creek Lodge, and when his car gets into a bad accident as a result of a bad blizzard, she manages to rescue him, taking his manuscript for his latest book along the way. She takes him to her isolated home and slowly nurses him to health, easing his pain with doses of Novril capsules, which causes Sheldon to eventually become addicted, and therefore easier to control. The drugs had another purpose, to act as stimulant in order to keep Sheldon's mind fertile in order to continue his writing. She is dangerously insane and bipolar, and has an averse reaction to profanity (her own vocabulary limited to child-like words such as cockadoodie). Her punishments grow more and more severe as she grows less complacent with Paul's behavior or slow progress. She first uses needles, then forcing Sheldon to drink soapy water, until eventually crushing or severing his feet and thumb. After Paul finishes the book, Annie plans a murder-suicide, but this is foiled when Paul burns a fake manuscript of Misery's Return (the real manuscript hidden under the bed) and then exhaustingly shoves charred pages down her throat before she trips on the typwriter and hits her head on the mantle. Paul is rescued, but then he realizes that she had survived his attacks, but succumbed to her head injuries after she crawled out to the barn, her hands wrapped around a chainsaw, intending to use it on Sheldon. Paul is then haunted by memories of her.The film's version of her death is a little different. The basic premise is the same. Paul distracts Annie by asking for another champagne glass and then douses the manuscript of Misery's Return in lighter fluid. He then lights a match, and when she protests, he tells her that he learned it from her and then lights the book on fire. She tries to put the book out, desperate to find out what happened to Misery, but to no avail. Paul then lifts up the heavy metal Royal typewriter above his head and drops it on Annie's head. Paul attempts to flee in his wheelchair, but Annie draws her Colt Cobra revolver and shoots Sheldon in the arm, then trying to strangle him. Sheldon gets the upper hand by pressing her eyes with his thumb and then tackling her onto the ground. Sheldon again gets the upper hand by shoving the burning pages down her throat in a failed attempt to strangle her. Annie kicks him in the crotch and attempts to flee, presumably to get another weapon, but Sheldon swings his leg out and trips her, causing her to fall headfirst onto the typewriter, presumably killing her. Sheldon crawls away, but Annie, barely alive, attempts to kill Paul for the last time. Paul gets the upper hand when he grabs the steel doorstop and beats her to death with it, fracturing her skull. A bloodied Annie looks at Paul with regret and then falls on top of him, dead.
Months later, back in his home in New York City, Paul is having lunch with his publicist, who asks if he would consider writing a nonficition book about his captivity at the hands of Annie Wilkes, to which Paul declines. Paul sees Annie momentarily, only to realize his mind was playing tricks on him and another woman is their waitress, implying he may be suffering from nightmares or hallucinations as a result of the ordeal.