On Halloween in Haddonfield, Illinois, having already shown signs of psychopathic tendencies, 10-year-old Michael Myers (Daeg Faerch) murders a school bully. Later that night, he murders his older sister Judith (Hanna R. Hall), his mother’s abusive boyfriend Ronnie (William Forsythe), and Judith's boyfriend Steve (Adam Weisman). Only his baby sister, Angel Myers, is spared. After one of the longest trials in the state’s history, Michael is found guilty of first degree murder and sent to Smith's Grove — Warren County Sanitarium under the care of child psychologist Dr. Samuel Loomis (Malcolm McDowell).
Kate and John Coleman (Vera Farmiga and Peter Sarsgaard) are experiencing strains in their marriage after their third child was stillborn. The loss is particularly hard on Kate, who is also recovering from alcoholism. The couple decides to adopt a 9-year-old Russian girl, Esther (Isabelle Fuhrman) from a local orphanage. While Kate's and John's deaf daughter Max (Aryana Engineer) embraces Esther immediately, their son Daniel (Jimmy Bennett) is less welcoming. Kate suspects that there might be problems in Esther's background when Esther's knowledge of sex extends beyond her age. Her suspicions deepen when Esther seriously injures another girl who had bullied her.
The plot involves an obsession with the 23 enigma, which is the idea that all incidents and events are directly connected to the number 23, or to some number connected to 23.
Tom Wingo (Nick Nolte), a teacher and football coach from South Carolina, is asked by his mother, Lila, to travel to New York to help his twin sister's psychiatrist, Susan Lowenstein (Barbra Streisand), after his sister Savannah's (Melinda Dillon) latest suicide attempt. Tom hates New York and reluctantly accepts, but largely to take the opportunity to be alone and away from a life that does not satisfy him. During his initial meetings with Lowenstein, Tom is reluctant to disclose many details of their dysfunctional family's secrets. In flashbacks, Tom relates incidents from his childhood to Lowenstein in hopes of discovering how to save Savannah's life. The Wingo parents were an abusive father and an overly proud, status-hungry mother. The father was a shrimp boat operator and, despite being successful at that profession, spent all of his money on frivolous business pursuits, leaving the family in poverty.
The emotionally withdrawn Joel Barish and the unrestrained free-spirit Clementine Kruczynski begin a relationship on a Long Island Rail Road train from Montauk, New York. They are almost immediately drawn to each other despite their radically different personalities.
Five French soldiers are convicted of self-mutilation in order to escape military service during World War I. They are condemned to face near certain death in the no man's land between the French and German trench lines. It appears that all of them were killed in a subsequent battle, but Mathilde, the fiancée of one of the soldiers, refuses to give up hope and begins to uncover clues as to what actually took place on the battlefield. She is all the while driven by the constant reminder of what her fiancé had carved into one of the bells of the church near their home, MMM for Manech Aime Mathilde (Manech Loves Mathilde; a pun on the French word aime, which is pronounced like the letter "M". In the English-language version, this is changed to "Manech's Marrying Mathilde").
Psychiatrist Jack Mickler (Marlon Brando) dissuades a would-be suicide—a 21-year-old, costumed like Zorro and claiming to be Don Juan (Johnny Depp), who is then held for a ten-day review in a mental institution. Mickler, who is about to retire, insists on doing the evaluation and conducts it without medicating the youth. "Don Juan" tells his story—born in Mexico, the death of his father, a year in a harem, and finding true love (and being rejected) on a remote island. Listening enlivens Mickler's relationship with his own wife, Marilyn (Faye Dunaway). As the ten days tick down and pressure mounts on Mickler to support the youth's indefinite confinement, finding reality within the romantic imagination becomes Jack's last professional challenge.
Predatory lenders Simone and Eddie awaken on either side of a room split by a cage containing a scale, wearing head harnesses with screws poised to pierce their temples. They learn via videotape that the one who sets more flesh weight on their tray will survive. Eddie cuts fat from his torso, but Simone chops off her arm, which tilts the scale in her favor; the timer expires, and Eddie is killed by the screws. While he reviews the game's footage, Detective Lt. Mark Hoffman is called to the scene by FBI Agent Dan Erickson, who found Agent Peter Strahm's fingerprints around the room. Also present is Agent Lindsey Perez, whose survival was covered up by Erickson for her protection. They learn from Dr. Adam Heffner, who performed all of the autopsies for the Jigsaw case, that the knife used to cut the jigsaw piece from Eddie's flesh was only used on Seth Baxter before then. The agents intend to find the Baxter videotape to prove Strahm's involvement.
The film opens in early 1980s Canada where teenager Martin Asher (Paul Dano) is seen ambling about a bus station, seemingly uncertain of his destination. He befriends another teen on the bus, Matt Soulsby (Justin Chatwin) and the two talk about their plans for the future. When their bus breaks down, the two acquire a car from a nearby garage. While Martin is driving, a tire blows. Matt struggles to change the tire and Martin comments on how he and Matt are both about the same height, and kicks Matt into the path of an oncoming truck. He is last seen toting Matt's guitar and walking away singing in a voice similar to Matt's.
Bob Wiley (Murray) is a good-natured man with great work ethic, but he suffers from multiple phobias and is divorced because his ex-wife is a fan of Neil Diamond. He feels good about the results of an initial session with Dr. Leo Marvin (Dreyfuss), a New York psychiatrist with a huge ego, but is immediately left on his own with a copy of Leo's new book, Baby Steps, when the doctor goes on vacation to Lake Winnipesaukee, New Hampshire for a month. Unable to cope, Bob follows Leo to his vacation home. Leo is annoyed because he does not see patients on vacation but, seeing how desperate Bob is, he gives Bob a prescription telling him to "take a vacation from his problems." Bob seems to have made a breakthrough, but the next morning shows up at Leo's house again and says that he decided to take a vacation both in spirit and in fact. He is staying on at Lake Winnipesaukee as a guest of the Guttmans, a couple who own a coffee shop and are more than happy to have Bob as their guest and encourage him to be around Leo, as they hold a grudge against him for purchasing the lakeside home they had been scrimping and saving for years to buy.
Emily Taylor's (Rooney Mara) husband Martin (Channing Tatum) is released after serving a four-year prison sentence for insider trading. Shortly afterward, Emily drives her car into a concrete wall in an apparent suicide attempt. Jonathan Banks (Jude Law), her assigned psychiatrist, fears for her safety but agrees to her release from the hospital as long as she attends sessions with him on a regular basis.
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 the final Misery novel. 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 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.
12-year-old Mark Evans (Elijah Wood) has recently experienced the death of his mother, Janice (Ashley Crow). Having been assigned for a business trip out of the country, Mark is taken by his father, Jack (David Morse), to stay with his uncle Wallace (Daniel Hugh Kelly) and aunt Susan (Wendy Crewson) in Maine. Mark is re-introduced to his extended family, including his cousins Connie (Quinn Culkin) and Henry (Macaulay Culkin). Mark and Henry get along at first, and Henry seems to be nice and well-mannered. In discussing the death of Mark's mother and that of Henry's baby brother Richard, however, Henry expresses an abnormal fascination with death, making Mark uneasy.
Washington, D.C. detective and forensic psychologist Alex Cross (Morgan Freeman) heads to Durham, North Carolina when his niece Naomi (Gina Ravera), a college student, is reported missing. He learns from the local police, including Detective Nick Ruskin (Cary Elwes), that Naomi is the latest in a series of young women who have vanished. Soon after his arrival, one of the missing women is found dead, bound to a tree in a desolate forest, and shortly after that, intern Kate McTiernan (Ashley Judd) is kidnapped from her home.