NOVA group members that were in the custody of NTAC escape from jail with outside help from Jordan Collier. Diana tells April about her relationship with Ben. Shawn and Richard learn that Isabelle is working with Dennis Ryland.

Someone is targeting young 4400's and Maia gets kidnapped. A mistake from Shawn's past comes back to haunt him. Richard is given a position of authority at the 4400 Center.

Tom is accused of murdering TJ Kim. 17 year old Boyd Gelder has the ability to change his appearance whenever he chooses. Meanwhile, Shawn and Isabelle grow closer.

Tom and Diana's investigation into a series of gruesome murders leads them to uncover another conspiracy within the government. At the 4400 Center, Shawn receives a gift from another returnee that allows him to see his future.

Ryland and other government officials are on trial for withholding vital information that they discovered about the returnees when a disturbing sound is heard the courtroom. Tom and Diana, with the help of Gary Navarro, try and track down T.J Kim, who they believe is responsible for the piercing sound heard in the courtroom. Richard and Lily are forced to deal with a now grown Isabelle While Lily also suffers from a rapid aging disease that Shawn is unable to heal. Tom and Diana also investigate a radical organisation called the Nova Group that appears to have ties with Shawn and the 4400 Center.

Gary Navarro is arrested for the second attempt to assassinate Dennis Ryland. Knowing she is the key to her mother's survival, Isabelle attempts to kill herself by jumping off the 4400 center building only to survive without a scratch. Matthew Ross expresses his displeasure at her actions and tells her of the destiny she is to face. Isabelle is troubled about what Matthew told her, but after a discussion with Shawn she decides it's her choice with what she does with her life. Matthew gives Isabelle a substance that can kill her if it's injected.

Kevin is on the run after horribly mutating due to the promicin experiments. Tom and Diana go to Tess for help. Diana gets what she believes is the flu and discovers something startling.

NTAC and the 4400 Center work together to find Jordan Collier. Kyle Baldwin gets a surprising visitor at the state prison.

Tom and Diana continue to investigate the disappearance of the 4400 children. Isabelle and Shawn's relationship becomes public.

Tom and Diana are drugged with a hallucinogen, that was created from oil that was secreted from the hands of a 4400.

Tom and Diana continue their investigation on Jordan Collier's plan for mankind. Dennis Ryland rejoins NTAC. Isabelle prepares for battle.

Isabelle seeks revenge on the Nova Group after they attack Shawn. Alana confronts the man responsible for killing her husband and son in a car accident nine years ago.

With the help of Dennis Ryland, NTAC track down the remining members of the NOVA group. Nikki pays Shawn a visit.