Isabelle is now a beautiful 20 year-old woman. Richard must contend with profound changes in both his daughter and his wife, who has turned 75. Tom and Diana track down a radical 4400 organization called the Nova Group.
Diana shows up at Tom's house to arrest him for murder. However, Tom hasn't been into work yet and has no recollection of what Diana is talking about.
A woman named Sarah Rutledge, who claims to be Maia's sister, approaches her and Diana at their house. Diana insists on a DNA test before the woman can spend any time with Maia, but Sarah kidnaps her while she is playing at a friend's house.
Maia has been erased by the people from the future, but Tom and Diana eventually begin to remember her and the other abducted 4400 children. They are able to locate, through history's pages, where and when in time the kids were sent, and each helped bring forth some advancement for humanity.
Shawn suffers from the mental illness inflicted upon him by the Nova Group. Isabelle wants revenge. Matthew objects to her wanting to retaliate, so Isabelle kills him.
Tom and Diana pursue Nova group member Gary Navarro, but he has been tipped off. The NSA has detained Alana, believing she has ties to the Nova Group.
Tom and Diana are drugged with a hallucinogen called Blink that was created by a 4400. Tom confronts his dead father, while Diana sees her ex-fiancee.
Kevin is forced to go on the run to protect his research on Promicin. We learn that he was using another 4400, Tess, to bring Diana to Kevin so he could inject her with Promicin without her consent.
A series of grizzly murders lead Tom and Diana to uncover a government conspiracy. Shawn recieves a special gift from a fellow 4400 - a cigar that when you smoke it, you see the future. Unfortunately, Shawn sees himself killing Richard.
Jordan Collier shows his face then disapears, leading the detectives on a manhunt. If they can find him alive, it proves that Tom's son Kyle didn't kill anyone.
Kyle tries to adjust to his new life out of prison. NOVA group members that were being held in NTAC custody escape with help from Jordan Collier. Diana admits to April that her and Ben are in a relationship. Shawn and Richard discover that Isabelle works for Dennis Ryland. Jordan tells others his plan - that he wants to give Promicin to everyone in the world.
Jordan Collier wants everyone in the world to inject themselves with Promicin, to save the future. However, Tom and Diana learn that Promicin has side effects. Fifty percent of people who take it will die. They try and stop him before thousands of people die.