Famed novelist Paul Sheldon (James Caan) is the author of a successful series of Regency romance novels featuring a character named Misery Chastain. Wanting to focus on more serious stories, he writes a manuscript for a new novel that he hopes will launch his post-Misery career. While traveling from Silver Creek, Colorado to his home in New York City, he is caught in a blizzard and his car goes off the road, rendering him unconscious. Paul is rescued by a nurse named Annie Wilkes (Kathy Bates), who brings him to her remote home. When Paul regains consciousness he finds himself bedridden, with both his legs broken as well as a dislocated shoulder. Annie claims she is his "number one fan" and talks a lot about him and his novels. As a reward for saving him, Paul gives Annie his new manuscript which she saved from the wreckage. While feeding him, she is angered by the profanity in the new manuscript and spills soup on him but regains control and apologizes. She buys a copy of Paul's most recently published book, Misery's Child, giving glowing praise to Paul as she progresses through the book. However, when Annie discovers that Misery dies at the end of the book she flies into a rage, almost smashing a table on Paul's head. She reveals that she lied about calling his agent and the authorities; nobody knows where he is. Annie leaves and Paul tries to escape from his room, but she has locked the door.
The next morning, Annie forces Paul to burn his latest manuscript. When he is well enough to get out of bed, she insists he write a new novel entitled Misery's Return, in which he brings the character back to life. Paul complies, believing Annie might kill him otherwise. He also tells her he will use Annie's name in the book in appreciation of her nursing him back to health. However, having found a way of escaping his room, he sneaks out when Annie is away and begins stockpiling his painkillers. He tries poisoning Annie during a candlelit dinner, but fails when she accidentally spills her drugged wine. During another venture out of his room, Paul finds a scrapbook of newspaper clippings about Annie's past. He discovers that she was suspected and tried for the deaths of several infants, but the trial crumbled due to lack of evidence. Paul also learns that Annie quoted lines he had written in his Misery novels during her trial. Annie later drugs Paul and straps him to the bed. When he wakes, she tells him that she knows he has been out of his room and breaks his ankles with a sledgehammer to prevent him from trying to escape again.
The local sheriff, Buster (Richard Farnsworth), is investigating Paul's disappearance. When a shopkeeper informs the sheriff he has sold Annie considerable quantities of typing paper, Buster surmises Paul must be at the Wilkes farm. Buster pays Annie a visit, who permits the sheriff to inspect the residence. When Buster finds Paul drugged and hidden in the basement, Annie fatally shoots Buster and tells Paul that they must die together. He agrees, on the condition that he must finish the novel in order to "give Misery back to the world". While she gets his chair, Paul conceals a can of lighter fluid in his pocket.
When the book is done, he reminds Annie it is his practice to have a single cigarette and a glass of champagne after finishing a novel. When Annie gives these things to Paul, he tells her that this time, he will need a second glass, for her. As Annie gets a second glass, Paul soaks the manuscript in the lighter fluid. When Annie returns with the glass he sets the manuscript on fire, giving him the chance to hit Annie over the head with the typewriter. Paul and Annie fight and Annie is killed.
Eighteen months later, Paul, now walking with a cane, meets his publishing agent Marcia (Lauren Bacall) in a restaurant in New York City. The two discuss his first non-Misery novel. Marcia tells him about the positive early buzz which Paul does not care about, saying he wrote the novel for himself. Marcia asks if he would consider a non-fiction book about his captivity, but Paul declines. While at the restaurant, he imagines the waitress as Annie. The waitress says she is his "number one fan", to which Paul uncomfortably responds "That's very sweet of you".
Output: What happens when Annie reaches the end of his manuscript for Misery's Child?