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.

Following the plane crash, the surviving heroes must team up with one another to try to survive the manhunt. Claire is quickly captured by Noah who takes charge of a "kill squad" to find the remaining people with abilities while Nathan deals with the overzealous 'hunter' Emile Danko whom becomes obsessed with tracking down all people with special abilities in his own lethal way. Mohinder and a powerless Hiro must rely on Matt Parkman's spiritual guide to help them. Daphne makes contact with Ando to help her find Matt, unaware of the people now targeting them. In New Jersey, Syler takes refuge in the house of an agent and tortures him to try to get information to what's going on and he forms an unlikely alliance with the agent's son Luke Campbell. Also, Peter teams up with Tracy to look for help, while she begins having second thoughts about running.