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After being home-schooled by her research zoologist parents in Africa for her entire academic life, Cady Heron moves to Evanston, Illinois and encounters the most dangerous habitat of them all: public high school.
She's quickly befriended by Janis and Damian, two outsiders who give Cady the lowdown on the social order at North Shore High. At the top of the social pyramid are Regina George and her two minions, Gretchen Wieners and Karen Smith, collectively known as "The Plastics."
When Regina spots Cady getting harassed in the cafeteria, she invites Cady to join The Plastics for lunch. Regina interrogates Cady and then The Plastics invite Cady to sit with them regularly, which, to them, is an honor on par with winning the Grammy for Best New Artist.
When Cady tells Janis about The Plastics' offer, Janis tells Cady she has to do it—and report back to her and Damian with all the moronic things the Plastics say. Janis and Regina have beef, but every time Damian tries to explain what it is, Janis cuts him off.
The following day, Cady goes undercover with The Plastics, and they lay down their ground rules for what Cady refers to as "Girl World," like how often they're allowed to wear their hair in a ponytail—you know, really important stuff. After much goading, Cady relents and tells Gretchen that she thinks Aaron Samuels is cute. Turns out that's Regina's ex, and, as Gretchen explains, that means he's off-limits.
After school, Cady and the Plastics end up at Regina's house, where the Plastics show Cady their Burn Book, a homemade book that includes an insulting and/or degrading page dedicated to each girl in their class. Cady's kind of horrified, and reports back to Janis and Damian with news of the Burn Book.
Shortly thereafter, Gretchen tells Regina that Cady likes Aaron. Regina gives Cady her blessing to pursue Aaron. Cady starts talking to Aaron more frequently at school, and he invites her to his buddy's Halloween party. Before Cady arrives at the party, Regina tells Aaron that Cady's basically a crazy stalker, then she comes on to him. They start making out. Cady sees them, leaves the party in tears, and heads directly to Janis and Damian. Together, they hatch a plan to end the reign of Regina.
First, they try various forms of physical sabotage, like replacing Regina's face wash with foot cream, but nothing seems to stick. Next, Cady sends a candy cane-gram to herself from Regina, so that Gretchen will get insecure when she sees that Regina didn't send her one, too. It works. Later, at the Winter Talent Show, Regina repeatedly snipes at Gretchen, and Gretchen cracks. Back at school, Gretchen starts spilling Regina's secrets to Cady, including the fact that she's cheating on Aaron with Shane Oman.
After Christmas Break, Cady, Janis, and Damian do everything they can to help Aaron catch Regina and Shane in the act. Nothing works. Then Cady turns Regina on to Kälteen bars, billing them as a carb-busting weight loss snack, when, really, they help you gain weight.
In the ensuing weeks, Cady starts failing her calculus assignments on purpose so Aaron will tutor her. At their first session, they kiss, and it looks like Cady's plan worked. When Aaron quickly reconsiders out of respect for Regina, Cady blurts out that Regina's cheating on him. Ouch.
As the Spring Fling approaches, Cady, Janis, and Damian continue their revenge plan, their focus now on severing Regina's hold on Gretchen and Karen. Damian stuffs the Spring Fling ballot boxes, so Gretchen gets nominated for Spring Fling Queen. While he's at it, he puts Janis in there, too. Cady and Regina round out the roster of nominees.
After class one day, Ms. Norbury stops Cady to tell her she's officially failing calculus, and encourages her not to dumb herself down for some guy. The Norbury calls herself a pusher. Later that afternoon, cheered on by The Plastics, Cady angrily adds a Ms. Norbury page to the Burn Book, where her being a "pusher" becomes her being a "drug pusher."
Cady calls Regina. Gretchen's secretly on the line, too, and Gretchen hears Regina say that Gretchen's not pretty enough to be Spring Fling Queen, and that it really should be Karen who's nominated, but she's too much of slut. Yeesh. Karen gets patched in, and Gretchen tells her what Regina said about her. The next day in the cafeteria, Gretchen and Karen let Regina have it, and Regina storms off. Gretchen and Karen promptly start following Cady around. She's the new queen bee.
That weekend, with her parents away, Cady throws a "small get-together" that turns into a monster party. Her anxiety goes through the roof, and she starts drinking. By the time Aaron arrives, she's drunk and makes a fool of herself. Regina busts in just in time to see Cady vomit on Aaron. He leaves, and Janis and Damian arrive. Janis had an art show that night that Cady blew off, and Janis is ticked. She tells Cady that she's not pretending to be plastic anymore; she is plastic.
Regina stomps back to her car, trailed by Shane, who tells her what Kälteen bars really are. That's the final straw. Regina goes straight home and adds a new page to the Burn Book, all about herself. The next day at school, Regina shows Mr. Duvall the Burn Book, claiming that Cady, Gretchen, and Karen created it because they're the only girls who aren't it. Then she throws photocopies of the book's pages all over the hallways. As soon as class is dismissed and her classmates see the pages, they go berserk and start fighting each other in the hallways—like legit hand-to-hand combat.
Mr. Duvall orders all the junior girls to the gym, and Ms. Norbury runs an impromptu, mandatory workshop that basically boils down to "How Not to Talk About People Behind Their Backs." Janis tells the entire group about her and Cady's plan to ruin Regina's life, and Regina storms out. Cady follows. In the street in front of the school, Regina lays the verbal smack-down on Cady and promptly gets hit by a bus.
Don't worry; she's okay.
That night, Cady's parents ground her for failing calculus. The next day at school, rumors fly that Cady shoved Regina in front of the bus. When cops show up in calculus to investigate Ms. Norbury's alleged drug dealing, Cady decides to take the blame for the Burn Book. Shortly thereafter, she aces a calculus test, apologizes to Ms. Norbury, and makes up with Aaron.
Ms. Norbury's not done with her yet, though; to make amends, she forces Cady to join the Mathletes. While the Spring Fling kicks off, the Mathletes kick a little numerical butt and win the State Championship. Then they go to the Spring Fling together, with Cady arriving just in time to be crowned Spring Fling Queen.
Cady gives a speech that boils down to "Making fun of other people doesn't make you any smarter, funnier, more attractive, etc." Aaron finds her on the dancefloor afterward and they share a kiss.
A quick look-ahead at senior year shows that everybody's getting along, the cliques have been shattered, and there's finally peace in Girl World.