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.

Paramedics try to resuscitate Susan Farrell. They believe that she took promicin and lost the 50/50 lotto that comes with it. Danny is certain that she did not take the shot. After arriving at the hospital with the paramedics, things get complicated as everyone around Danny start to die. Garrity and another NTAC agent are sent to the hospital to assess the situation.

A morbid premonition from Maia threatens the future of 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.

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

Jordan wants Shawn to rejoin the movement. Meanwhile, a 4400 with an amazing ability disappears.

Diana helps Tom break Kyle out of NTAC quarantine, eventually leading them to discover the truth behind the 4400.

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.

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.

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.

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.

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

Tom tracks Jordan to a small town, where he meets a woman who can relieve people's stress by talking to them. Meanwhile, Marco and Diana have a nice talk. Maia's visions are giving her nightmares.

NTAC races against the clock to stop a group of fanatics targeting 4400s.

A 4400 terrorist releases a signal at NTAC that makes the men violent, forcing a lockdown of the facility. Lilly questions how the Centre is handling her daughter, and Shawn tries to recruit a familiar face.

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

Jordan Collier's movement takes a huge step forward when his followers settle in the heart of Seattle.

Meghan and Diana learn how to remove the entity from Tom, but the procedure is dangerous. Meanwhile, Shawn finds help in his attempt to rescue Kevin from Promise City; and Jordan is betrayed by someone close.

Tom and Diana investigate a mysterious structure being built at a psychiatric hospital, based on the drawings of one of their patients who's a 4400.

NTAC is keen to find Jordan Collier's killer as Tom is desperate to find Kyle.

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

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'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.

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.

Audrey Parker, an elderly woman, takes promicin and develops the ability to astral project. Meanwhile, Shawn decides to start publicly healing people again despite threats from the government to shut him down. And Ben and Maia return to Seattle to visit Diana.