Bianca (Mae Whitman) is enjoying her senior year of high school with two close friends Jess (Skyler Samuels) and Casey (Bianca Santos) who are significantly more popular than she is. She is also the neighbor and former childhood friend of Wesley "Wes" Rush (Robbie Amell), a star on the school's football team, with whom she has fallen out during high school. She has a crush on guitar-playing Toby Tucker (Nick Eversman), and reluctantly attends a party hosted by mean-girl Madison Morgan (Bella Thorne), hoping to talk to him. The party turns out to be a disaster for her, as it's there that Wes unthinkingly reveals to her that she is the "DUFF" of her friend group, the "Designated Ugly Fat Friend." The DUFF does not actually have to be ugly or fat, he explains, it's just the person in a social group who is less popular and more accessible than the others in the group. People exploit The DUFF to get to the popular people.
Tripper Harrison (Murray) is the head counselor of a group of new counselors-in-training (CITs) at Camp North Star, a cut-rate summer camp. Camp director Morty Melnick (Atkin) falls victim to Tripper's practical jokes mainly by being taken from his cabin in the middle of the night and being relocated to an unusual place such as in a hammock above the trees or along the roadside outside of camp.
High school senior Andie Walsh (Molly Ringwald) is a working-class girl who has a crush on one of the rich, preppy boys in her school, Blane McDonough (Andrew McCarthy). When Andie and Blane try to get together, they encounter resistance from their respective social circles. Andie lives on "the wrong side of the tracks" with her underemployed father, Jack (Harry Dean Stanton). Andie's best friend, Phil "Duckie" Dale (Jon Cryer), is in love with her, but plays it off as a joke in front of her. In school, he and Andie are harassed and bullied by Blane's friends, the arrogant so-called "richie" kids, Benny (Kate Vernon) and Steff (James Spader). Steff is especially interested in Andie, but she finds him repellent and continuously brushes him off. Andie works at TRAX, a new wave music store, managed by her older friend and mentor Iona (Annie Potts). Iona advises Andie to go to her senior prom despite not having a date.
Shermer, Illinois, is a fictitious suburb of Chicago. There, nerdy social outcasts Gary Wallace (Anthony Michael Hall) and Wyatt Donnelly (Ilan Mitchell-Smith) are publicly humiliated by Ian (Robert Downey, Jr.) and Max (Robert Rusler) after they are seen swooning over two girls who happen to be their girlfriends. Dejected and disappointed at their direction in life and wanting more, Gary convinces the uptight Wyatt that they need a boost of popularity in order to get their crushes, Hilly (Judie Aronson) and Deb (Suzanne Snyder), away from Ian and Max. Alone for the weekend with Wyatt's parents gone, Gary is inspired by the 1931 classic Frankenstein to create a virtual girl using Wyatt's computer; infusing her with everything they can conceive to make the perfect dream girl. After hooking electrodes to a doll and hacking into a government computer system for more power, a power surge creates Lisa, a beautiful and intelligent woman with seemingly endless powers. Promptly, she conjures up a Cadillac convertible to take the boys out to a bar, using her powers to manipulate people into believing Gary and Wyatt are of age. The boys come up with the name Lisa (Kelly Le Brock), based upon a failed romantic experience of Gary's that ended with Lisa kicking him in the testicles.
Recent graduates of Georgetown University Alec, girlfriend Leslie, Kevin, Jules, and Kirby are waiting to hear about the conditions of their friends Wendy, a sweet-natured girl devoted to helping others, and Billy, a former frat boy and now reluctant husband and father, after a car accident. At the hospital, Kirby sees a medical student named Dale, with whom he has been infatuated since college.
In 1965 Tulsa, Oklahoma, Greasers are a gang of tough, low-income working-class teens. They include Ponyboy Curtis (Howell) and his two older brothers, Sodapop (Lowe) and Darrel (Swayze), as well as Johnny Cade (Macchio), Dallas Winston (Dillon), Two-Bit Matthews (Estevez), and Steve Randle (Cruise). Their rivalry is with the Socs (pronounced /ˈsoʊʃɪz/ soh-shiz), a gang of wealthier kids from the other side of town. Two Socs, Bob Sheldon (Garrett) and Randy Adderson (Dalton), confront Johnny, Ponyboy, and Two-Bit, who are talking to the Socs' girlfriends, Cherry (Lane) and Marcia (Meyrink), at a drive-in theater. The girls defuse the situation by going home with the Socs. Later that night, Ponyboy and Johnny are attacked in a park by Bob, Randy, and three other Socs. They begin dunking Ponyboy in a fountain, but Johnny pulls out his switchblade and stabs Bob, accidentally killing him.
Michael Emerson (Jason Patric) and his younger brother, Sam (Corey Haim), move with their recently divorced mother, Lucy (Dianne Wiest), to the beach community of Santa Carla, California. The family moves in with Lucy's father (Barnard Hughes), a cantankerous and eccentric old man who lives on the outskirts of town and enjoys taxidermy as a hobby.
Ambitious high school senior Matthew Kidman (Emile Hirsch) has been accepted to Georgetown University, but cannot afford the tuition. He has raised $25,000 in order to bring a brilliant Cambodian student, Samnang, to study in the United States, but finds little else truly memorable about his high school experience. His life suddenly changes when charismatic Danielle (Elisha Cuthbert) moves in next door. Matthew witnesses her undressing from his bedroom window, until she sees him and storms over, knocking on the door and introducing herself to his parents. They suggest to Matthew that he show Danielle around town.
Ronald Miller (Dempsey) is a typical high school nerd living in Arizona. He has spent all summer mowing lawns to save up for a telescope. However, at an opportune moment he makes a deal with popular cheerleader Cynthia "Cindy" Mancini (Peterson) to "rent" her for $1,000. Cindy borrows a suede outfit that belongs to her mother, without her permission, and needs to replace it quickly after Quint (Cort McGown) accidentally spills red wine on Cindy at a party. Having few options except telling her Mom the truth, she reluctantly agrees to help him look "cool" by pretending to be his girlfriend for a month, even though she already has a boyfriend named Bobby who is away at his freshman year at the University of Iowa. Both agree never to reveal their financial arrangement.
Anita "Needy" Lesnicki, once an insecure and bookish teenager living near Devil's Kettle, Minnesota, is now a violent mental inmate who narrates the story as a flashback while in solitary confinement. She has been friends with a selfish and popular cheerleader, Jennifer Check, since childhood, despite having little in common. One night, Jennifer takes Needy to a local dive bar to attend a concert by indie rock band Low Shoulder. A suspicious fire engulfs the bar, killing several people, and Jennifer, who is in shock, agrees to leave with the band despite Needy's protests. Later that evening, Jennifer, covered in blood, appears in Needy's kitchen and proceeds to eat food from the refrigerator. Unable to digest the matter, she vomits a trail of black, spiny fluid and then leaves in a hurry as Needy calls after her.
Lola (Christa Theret) is a pretty teenage girl living with her mother Anne (Sophie Marceau), who is divorced from Lola's father, Alain (Alexandre Astier). Nicknamed "LOL" by her friends, Lola has been taking her first steps into teenage romance, dating a boy from her class named Arthur (Felix Moati). Following the summer break, Lola's life becomes complicated when Arthur tells her that he cheated on her over the summer and was dating her friend, Lvis. Lola decides to break things off with him and start seeing his close friend Mael (Jeremy Kapone). Lola's friends seem to enjoy complicating matters even more. Life at home has also become impossible with her mother, who has no idea what "LOL" means. She treats her teenage daughter like a child, wondering whatever happened to her sweet little daughter. Lola likes to play her mother and father against each other for her own advantage, but what she doesn't know is that Anne and Alain have begun dating again on the sly.
Nancy Drew (Emma Roberts) and her widowed father, Carson Drew (Tate Donovan), move from River Heights for only a few months and rent a house in California, where Carson has a temporary job. Nancy chose their California house because it was the home of Dehlia Draycott, a murdered movie star based on Natalie Wood whose case has never been solved. Despite the mystery, Nancy's father has forbidden her from further sleuthing and encourages her to focus on high school and living like a normal teenager. Nancy struggles to fit in at her new school, only befriending a younger boy, Corky (Josh Flitter). She realizes that the sleuthing world is the only place she fits in and decides to solve the Draycott mystery behind her dad's back. In the Draycott mansion, she discovers a letter that Draycott wrote to an unknown "Z," who was supposedly Draycott's lover. From photographs of Draycott before her death, Nancy deduces that, just before Draycott was murdered, she had a baby and secretly gave it up for adoption. Nancy eventually finds Draycott's child, who turns out to be a young single mom named Jane Brighton, and who also turns out to be the sole beneficiary of Draycott's will, which has disappeared. Nancy receives a threatening phone call telling her to get off the case, and contacts her father's business associate, Dashiel Biedermeyer (Barry Bostwick), the lawyer of the Draycott estate, to assist her with the case.
Erik Stifler (John White) has a difficult time living up to his family name. He is Steve and Matt Stifler's cousin. He is perhaps the only Stifler about to graduate from high school as a virgin. The film opens with Erik feigning illness so that he can stay home and masturbate. Unfortunately, just as he is about to ejaculate, his parents and grandmother unexpectedly walk into the door and are hit with Erik's semen, after which his grandmother dies of a heart attack. Erik's dad later surmises that, as a Stifler, his son should be out having sex instead of masturbating. Erik's girlfriend of two years, Tracy (Jessy Schram), loves him, but is not ready for intercourse. Tracy decides to have sex, their first attempt goes horribly wrong, and she backs out of trying again.
Brad Hamilton is a popular senior who is looking forward to his last year of school and almost has his 1960 Buick LeSabre paid off. He has a part-time job at a burger joint, "All American Burger" where his girlfriend, Lisa, also works. This esteemed establishment has a strict policy of etiquette: "No Shirt, No Shoes, No Dice". He is pondering how to end his relationship with Lisa so he can play the field during his senior year. However, Brad is fired for losing his temper at an obnoxious customer; when he tries to tell Lisa how much he needs her, she says she is dumping him to see other guys. Brad quits his next job at Captain Hook Fish & Chips because of the humiliation of having to wear a pirate costume when delivering food. He gets a job at a convenience store, Mi-T-Mart, where he successfully thwarts an attempted robbery and is promoted to store manager.
Four friends — Chloe (Skyler Shaye), Yasmin (Nathalia Ramos), Sasha (Logan Browning), and Jade (Janel Parrish) — are about to start high school. Self-centered Meredith Eilazbeth Vickrica Baxter Dimly (Chelsea Kane) wants everyone to belong to a clique, and goes about organizing people. She does not like the independent spirit of the four girls and plots to destroy their friendship and make them conform to her pre-fabricated cliques. Chloe is an amazing soccer player. She meets Cameron (Stephen Lunsford) and is instantly smitten. Sasha is recruited as a cheerleader. Jade joins the science kids and meets Dexter (Chet Hanks) and designs great outfits. Yasmin joins journalism, even though her real passion is singing even though she hasn't realized yet. She also feels lonely as her friends are busy with their own cliques. She also meets Dylan (Ian Nelson), who is deaf but can lip read. The friends begin to drift apart, as they are compelled to stay within their cliques. Two years later, when an accidental food fight causes them to get detention, they realize that they miss being BFFs and decide to be friends again. They also try to get the other schoolmates to socialize outside their cliques, but their attempts fail when Meredith's 2nd Super Sweet 16 party (which ends disastrously) has them seated with their original cliques. The upcoming talent show and its prize of a scholarship gives them the idea to bring all the cliques together again with an act, but the chances are slim with Meredith's constant attempts to steal the spotlight. In the end, there is a tie. Meredith gets the trophy, but the girls get the scholarship, which they later give to Cloe.