John Smith (Alex Pettyfer) is an alien from the planet Lorien. He was sent to Earth as a child with eight others to escape the invading Mogadorians, who destroyed Lorien. Here, John is protected by a Cepan, or guardian, Henri (Timothy Olyphant). Together, they live in a beach-side bungalow in Florida.
When the film opens, a St. Bernard puppy and a large group of others are stolen from a pet store by two thieves, Harvey (Oliver Platt) and Vernon (Stanley Tucci). After meeting a dog during his escape from the thieves, the St. Bernard sneaks into the home of the Newton family. The workaholic father, George Newton (Charles Grodin), doesn't want the responsibility of owning a dog, but his wife, Alice (Bonnie Hunt), and their children, Ryce, Ted and Emily, convince him otherwise. While trying to name him, Emily (Sarah Rose Karr), plays a portion of Ludwig van Beethoven's Fifth Symphony and he barks along: thus they name him "Beethoven."
Jesse "Jess" Aarons (Josh Hutcherson) is a twelve-year-old aspiring artist living with his financially struggling family in Lark Creek. He rides the bus to school with his little sister May Belle (Bailee Madison), where he avoids the school bully Janice Avery (Lauren Clinton). In class, Jess is teased by classmates Scott Hoager (Cameron Wakefield) and Gary Fulcher (Elliot Lawless), and meets new student Leslie Burke (AnnaSophia Robb). At recess, Jess enters a running event, for which he had been training at home. Leslie also enters and manages to beat all the boys, much to Jess' irritation. On the way home, Jess and Leslie learn that they are next-door neighbors.
Sixteen-year-old homeschooled Cady Heron (Lindsay Lohan) and her zoologist parents (Ana Gasteyer and Neil Flynn) return to the United States after a 12-year research trip in Africa, settling in Evanston, Illinois. Cady attends a public school for the first time, meeting new classmates Janis (Lizzy Caplan) and Damien (Daniel Franzese). The two warn Cady to avoid the school's most exclusive clique, the Plastics, who are led by queen bee Regina George (Rachel McAdams). The Plastics take an interest in Cady, however, and start to invite her to sit with them at lunch. Seeing that Cady is slowly becoming one of The Plastics, Janis hatches a plan of revenge against Regina, using Cady as the infiltrator.
Will Freeman (Hugh Grant) lives a serene and luxurious lifestyle devoid of responsibility in London thanks to substantial royalties left to him from a successful Christmas song composed by his father. Will begins attending a support group for single parents as a way to meet women and as part of his ploy, invents a two-year-old son named Ned. His plan succeeds and he meets Suzie (Victoria Smurfit). Will brings Suzie on a picnic where he meets Marcus (Nicholas Hoult), the 12-year-old son of Suzie's friend, Fiona (Toni Collette). Will gains Marcus' interest and trust after he lies to a park ranger to cover up for Marcus killing a duck. Afterward, when Will and Suzie take Marcus home, they find Fiona in the living room, overdosed on pills in a suicide attempt.
Attorney Mitch Martin (Luke Wilson) breaks up with his girlfriend when he accidentally discovers that she takes part in orgies. Mitch encounters his high school crush, Nicole (Ellen Pompeo), at the wedding of his friend Frank (Will Ferrell) and makes an awkward impression. Later, he finds a house located near the campus of the fictional Harrison University in New York.
Alone in her home, the religion-obsessed Margaret White (Julianne Moore) gives birth to a baby girl. She at first intends to kill the infant, but changes her mind. As a teenager, her daughter Carrie (Chloë Grace Moretz), is a shy and isolated student at Ewen High School in Maine.
Ludo Decker (Schweiger) is a Berlin based yellow press reporter. With his photographer Moritz, his daily routine is to spy on celebrities for the tabloid Das Blatt. He also uses his work for frequent sexual contacts with his objects of interest.
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 first day of Greg Heffley's middle school ends negatively; he learns about the Cheese Touch which is a rotten piece of cheese on the basketball court which everyone avoids, discovers the ups and downs to the school, and his best friend Rowley Jefferson (Robert Capron) embarrasses them both. He plans to become extremely popular, which results in two humiliating defeats joining the wrestling team by a weird, low popular kid named Fregley (Grayson Russell) and his arch-enemy Patty Farrell (Laine MacNeil). Later. Greg makes it an effort to make Rowley popular by changing his style of clothing and looks, and they also encounter delinquent teenagers at Halloween night in which they challenged.
The Heffley family attends a pool party at the local pool, where the family meets a former trouble-making friend of Rodrick (Devon Bostick) who is now a model student after attending a military school known as Spag Union, into which Greg's dad Frank (Steve Zahn) thinks about joining Greg.
The Heffley family attend a party at a roller rink, where Greg (Zachary Gordon) reunites with Rowley (Robert Capron), meets a new girl at school named Holly Hills who Greg instantly has a crush on, and reveals he passed on the Cheese Touch. Rodrick interferes with the party, embarrassing Greg as he describes his summer and the flaws between his brothers.
Max (Cayden Boyd) is a lonely child in the suburbs of Austin who creates an imaginary world named Planet Drool, where all of his imagination and dreams come to life. He creates two characters; Sharkboy (Taylor Lautner), a young boy who was raised by sharks after losing his father at sea, and Lavagirl (Taylor Dooley), who can produce fire and lava, but has trouble touching objects without setting them alight. The two left Max to guard Planet Drool. In real life, Max's parents (David Arquette and Kristin Davis) have little time for him and their marriage seems to be on the rocks, and he is bullied by fellow schoolmate Linus (Jacob Davich). However, he does receive friendship from Marissa (Sasha Pieterse), the daughter of his teacher Mr. Electricidad (George Lopez, whose name is Spanish for "electricity"). Linus steals Max's Dream Journal (where all of his ideas are kept) and vandalizes it. The next day, a tornado rages outside the school, and moments later, Sharkboy and Lavagirl appear and ask Max to come with them to Planet Drool. They reach Planet Drool via a shark-like spacecraft, where Max learns that the dreamworld is turning bad, courtesy of Mr. Electric (also portrayed by George Lopez), originally the dreamworld's electrician but now corrupted.
On the night of October 31, 1963, in Haddonfield, Illinois, 6-year-old Michael Myers (Will Sandin) murders his older sister Judith (Sandy Johnson) by stabbing her with a kitchen knife. Fifteen years later, on October 30, 1978, Michael escapes Warren County Smith's Grove Sanitarium, where he had been committed since the murder. He steals the car that was to take him to a court hearing, the intention of which was for him to never be released.