The Community General doctors are dragged back into the world of network television when producer Jackson Burley revamps the pilot for Dr. Danger, the television program based on Dr. Sloan. Mark and Steve investigate when Danger's competition, a masked magician who reveals the profession's secrets, is murdered, possibly as a ratings ploy.
Steve enlists troubled teenager (he sure looked older than a teenager) Tommy to work as community service at a boxing club after too many brushes with the law. Tommy tries to control his temper. Mark finds that the club's sports drink is drugged, promoting aggressive tendencies in many of the boxers.
Jesse saves a woman, Chloe, in a traffic accident that claims a jealous lover forced her off the road. Jesse looks out for his patient when her ex-boyfriend threatens her. Jesse rushes to Chloe's aid when her life is threatened by her boyfriend, and inadvertently kills him. Jesse finds himself the victim of Chloe's 'fatal attraction' as she pursues him voraciously. It gradually becomes clear that Chloe was the aggressor in her previous relationship.
Mark, Jesse, and Amanda are trapped in a hotel when it's quarantined after a deadly virus is released. They struggle to contain the virus, while at the same time trying to locate its origin. Meanwhile, a scheming seductress carries out her plan, using the virus as a diversion to rob a nearby bank vault.
Newly retired detective Harry Trumble returns to the force when it appears 'The Clown Killer', a murderer Trumble chased for more than a decade, has emerged from obscurity to kill again. Mark is reluctant to help Harry investigate the Clown, in part due to a rift between the two, but also because Mark suspects Harry has something to do with the Clown's reappearance.
Jesse's car breaks down while he and Susan are on their way to a fun-filled vacation in Carmel. The two are stranded in a small town where Susan spies a supposedly long dead beau, Greg. They eventually discover that he faked his death in order to plunder a shipwrecked vessel undetected. The townsfolk, all in on the scheme, murder Greg and pin the blame on Jesse and Susan.
Steve and his abrasive, confrontational partner are confined to a therapy home for 90 days after Steve shoots and kills a fleeing suspect. Steve's partner, Reggie, believes his wife and daughter are being held hostage by his nemesis, a belief that is furthered by a series of delusional events. On the outside, Jesse and Amanda work with Tanis Archer to solve the murder of a lab technician.
The hospital is the scene of a manhunt when a corpse comes to life and attacks Amanda, then leads Steve and the police on a chase throughout the entire building during which he kidnaps Jesse's girlfriend Steve. Mark learns the fugitive is on the run from NSA agents, who claim he's an international terrorist.
Mark, Steve, Jesse, and Amanda are all trapped in the rubble of Community General in the aftermath of the bombing. Mark tries to shake off the numbing effects of the explosion in time to save Amanda, who's suffering from a punctured lung and broken collarbone. After the dust settles, the hunt for Caitlin Sweeney begins. It's discovered that the Sweeneys belong to a terrorist organization, R.O.A.R.