4400 people, assumed to be dead or missing over the past fifty years, reappear in a ball of light. None have any memory of where they've been, and some are manifesting paranormal abilities.

Tom and Diana investigate a 4400 who has used his ability of enhanced reflexes to become a vigilante.

Tom and Diana investigate a 4400 junior high school teacher accused of child abuse.

A morbid premonition from Maia threatens the future of the 4400 Center.

When 4400s around the world come down with life-threatening illnesses, Ryland comes back to NTAC and orders the sick - and even unaffected 4400s - to be quarantined. Tom and Diana race to find a cure and discover a shocking secret in the process.

Discovering that NTAC is behind the disease plaguing the 4400s, Tom and Diana try to get to the bottom of NTAC's cover-up, while Kyle considers turning himself in.