Two months after the destruction of both the Primatech and Pinehurst, and the death of Arthur Petrelli, the now-villainous Nathan returns with a vengeance by persuading the U.S. President and the government to round up all people with abilities for containment and disposal, leading to Claire, Ando, Peter, as well as Tracy to become fugitives from the people who were their former allies. In Japan, a powerless Hiro tries to live through the super-charger Ando as his latest partner. In New York, Peter struggles to find a life for himself as a paramedic, but finds that his cannot hide from his past. Claire learns about Nathan's and Angela's plans for interment of people with abilities and sets out to warn Matt Parkman who learns more about his abilities from the spirit of the African spiritualist Usutu. Elsewhere, Syler travels to Baltimore to locate his long-lost father and ends up being the only one who escapes from a government dragnet led by a mysterious agent known only as 'the Hunter'. Mohinder also learns that he has been targeted, and that Noah Bennett is apparently working with Nathan as well.

Imprisoned inside the super-secret 'Building 26' which is Nathan's base of operations to experiment and terminate people with abilities, Tracy struggles to survive various "heat" experiments as well as wait for an opportunity to try to escape. While the ruthless Hunter Davko obsessively continues to track down the heroes with the obsession of killing them all, Nathan deals with the President of the USA who begins to investigate Nathan's activities and tactics to hunt down the "targets". Meanwhile, Syler continues his quest to locate his biological father with both help and inference from Luke Campbell, as well as government agents now after both of them. Hiro, Ando, and Matt travel to India to find a new ally with abilities to help them survive. In California, Claire faces the wrath of her father.

The identity of "Rebel" is revealed with chilling consequences - Emmy Award-Winner Zeljko Ivanek, Brea Grant and Swoosie Kurtz Guest Star.

Claire, back home in California, begins attending college, but is having difficulty adjusting when a mysterious death of a student during the orientation puts her back in the spotlight. In Japan, Hiro and Ando continue their quest to help people with abilities and go so much as to advertise themselves. Meanwhile, Angela fears Nathan/Syler will discover his true identity. Matt tries to settle down back in Los Angeles and raise his son and not worry about unexpected visitors. Elsewhere, Peter is using his ability for good when a mysterious carnival clan, led by Samuel Sullivan, arrives in town which could spell trouble for him and everyone else.