Hayley comes home from a Green Party rally with her hair dyed green, instigating a fight with Stan. While she's sleeping, Stan cuts her hair (for her own good, of course). After learning of what Stan did, a wigged Hayley defies her father yet again by moving into the van of her new boyfriend. When Stan cuts her off financially, she gets a job as a waitress in a strip club, which pushes Stan right off the edge. Meanwhile, Steve tries to pass Roger off as his disfigured sister in order to cop a feel with a female classmate.
Brian becomes a substitute teacher at Chris' school after his teacher wins the lottery. When Brian is moved to teach a class of troubled kids, Chris falls in love with his new teacher, Mrs. Lockhart, who promises to love Chris only if he kills her husband. When Lois finds out, she and Stewie decide to teach Chris a lesson.
Derek and Meredith try (unsuccessfully) to be discreet as they spend the night together at Meredith's house, but their haggard appearance speaks volumes to everyone - including Bailey, who warns Meredith to end the relationship. Meanwhile George suspects an anesthesiologist of drinking on the job but is reluctant to speak up about it, Alex treats a former competitor who now finds honor in self-mutilation, Izzie has to deal with a patient who won't let go of his girlfriend - literally, and Cristina seems to be battling a case of the flu.
Homer sees a movie about the end of the world and fears the same thing will happen in real life after seeing a chain of random occurrences and doing a complicated math equation that predicts the end will come on May 18th.