Working with Cody again following their collaborative efforts on the film Juno, Jason Reitman stated he and his producers "want to make unusual films". Cody said she wanted the film to speak to female empowerment and explore the complex relationships between best friends.
The film had a lackluster performance at the North American box office, making $2.8 million its opening day and $6.8 million its opening weekend, and received mixed reviews from critics; whereas negative reviews criticized the narrative and, specifically, the horror/comic premise for "fail to be either funny or scary enough to satisfy", positive reviews praised the film for its dialogue, Megan Fox's and supporting performances, and emotional resonance.
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. Since childhood, she had been friends with a selfish and popular cheerleader, Jennifer Check, 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. In shock, Jennifer 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 it, she vomits a trail of black, spiny fluid and then leaves in a hurry as Needy calls after her.
The next morning at school, Jennifer appears fine and shrugs off Needy's concerns. While the whole town is devastated by the deaths caused by the fire, Jennifer seduces the school's football captain in the woods and then kills him; his disemboweled corpse is later found. Meanwhile, the members of Low Shoulder gain popularity due to their rumored heroism during the fire and offer to make a charity appearance at the school's spring formal.
A month later, Jennifer is beginning to look pale, so she accepts a date with school goth/emo Colin, whom she brutally kills. While Needy and Chip have sex, Needy senses something dreadful has happened. She leaves in a panic and almost runs over Jennifer, who is drenched in blood. At home, she finds Jennifer in her bedroom. Jennifer kisses her, initiating a brief makeout session, and soon explains what happened after the fire: Low Shoulder took her into the woods and offered her as a virgin sacrifice to Satan in exchange for fame and fortune. Although the sacrifice and demonic exchange were a success, Jennifer was not a virgin. As a result, when lead singer Nikolai murdered her, the ritual backfired and a demonic spirit took over her body. Unbeknownst to Needy, Jennifer also encountered Indian exchange student Ahmet after the fire and, upon hearing that no one knew he had survived, took him into the woods and made him her first victim. Jennifer states that when she has eaten, she can withstand virtually any injury without pain, making her rather difficult to kill.