Everyone on Earth is excited about a comet passing by, but as soon as its trajectory changes to a collision course, everyone starts to panic. The comet turns out to be a giant ball of light that, after exploding, leaves behind 4400 people. They are missing persons who have been gone from a few months to 60 years, and none have aged a day. The 4400 are put in quarantine and eventually released. Some of the returnees begin to exhibit strange and uncontrollable new abilities. Tom Baldwin and Diana Skouris, two Homeland Security agents, are appointed to find out what happened to the 4400.
Carl Morrissey is a lowly supermarket employee who happens to be one of the 4400 returned abductees. He uses his new found powers - enhanced reflexes and strength - to become a vigilante and fight crime in his neighborhood. Meanwhile, Lily is thrown in jail for violating the restraining order while looking in on her daughter and ex-husband's new life. After picking up Lily from the police, Richard and Lily go back to the apartment they now share and we see the romance between the two begin to become more serious. Also, Shawn begins to learn more about his healing powers, and we are left with a cliffhanger ending of whether he will heal his cousin.
Tom and Diana are sent out to investigate a homicide that resembles the MO of a serial killer who was never caught nor heard of for 21 years. The first suspect is Oliver Knox, a member of the 4400. However, Knox has an alibi for the night of the murder and another man confesses to all the crimes. Tom and Diana suspect that Knox is luring people to kill for him and try to lay a trap on him. Meanwhile, people begin to turn hostile toward the 4400, and Jordan Collier decides to organize his fellow returnees. But Richard feels uneasy about Collier's interest in them.
The 4400 are attacked by a series of fire-bombings after Barbara Yates made their names and addresses known to the public. Tom, Diana, and Ryland try to put an end to the bombings at the same time as Tom tries to deal with the disturbing behavior of Kyle, and Diana tries real hard to be a good substitute mother to Maia. However, the arrival of a Homeland Security agent from Washington, Warren Lyttel, makes their work even harder. Jordan Collier tries to provide his followers with safe shelter, but Richard and Lily begin to question his intentions as the bombings intensify.
Tom is furious upon finding out that Lyttel took his son Kyle into custody. Diana offers him help in getting Kyle back. Meanwhile, Richard suspects that Collier is trying to take control of Lily's life, and as soon as Collier reveals his intentions, Richard and Lily leave Arcadia Estates. Elsewhere, Danny snaps at Shawn when he finds out that he and Nikki have slept together. Tom and Diana finally find out what really happened to the 4400, which leaves a disturbing question: is this the end - or just the beginning?
It's been one year since the 4400 returned. After a period of intense medical observation, Tom has returned to NTAC in a limited capacity, assigned only to desk duty. Diana, having been through a series of inept partners, finally finds a way to cut through the red tape and get Tom back, all while in the midst of formally adopting Maia. Meanwhile, Richard, Lily and the baby are still living in meager conditions in a mountain cabin far away from Jordan. Jordan has now closed Arcadia Estates, and is on the verge of opening "The 4400 Centers," a place for non-members of the 4400 to discover "the 4400 within themselves." Collier becomes Shawn's guardian, and enlists him to heal important benefactors of the Centers.
It's been one year since the 4400 returned. After a period of intense medical observation, Tom has returned to NTAC in a limited capacity, assigned only to desk duty. Diana, having been through a series of inept partners, finally finds a way to cut through the red tape and get Tom back, all while in the midst of formally adopting Maia. Meanwhile, Richard, Lily and the baby are still living in meager conditions in a mountain cabin far away from Jordan. Jordan has now closed Arcadia Estates, and is on the verge of opening "The 4400 Centers," a place for non-members of the 4400 to discover "the 4400 within themselves." Collier becomes Shawn's guardian, and enlists him to heal important benefactors of the Centers.
Gary Navarro, a minor league baseball player back after a 30-year absence, finds that hearing everyone's unspoken thoughts is driving him to the edge of madness. When he seeks help from NTAC, the higher-ups are more interested in how he can unearth information about Jordan Collier than how they can assist Gary with getting his life back. As the case occupies the majority of his time, Tom finds himself struggling with his responsibilities as a single father. Meanwhile, Kyle starts to get his life back through the prospect of a new relationship, Diana finds herself dealing with the unexpected arrival of her younger sister April, and as Richard, Lily, and Isabelle continue their life on the run, Richard grows increasingly disturbed by his daughter's apparent abilities.
Someone puts his 4400 ability up for auction, and the Supreme Court will have a special session to determine if it's legal and if the auction can continue. Diana and Tom are ordered to investigate. Meanwhile, pop diva Chloe Granger is at the 4400 Center and claims that Jordan's book was a revelation to her. She even cut her tour short because she felt she needed to come to the 4400 Center and become a student. Jordan makes sure this new "recruit" is well treated as it will profit the center. Shawn is working on a recruitment video for the 4400 Center. Richard and Lily travel to Montana where they meet with Eric Papequash, who disappeared in 1955.
A school teacher terrifies parents with her supernatural ability to inspire artistic students. Meanwhile, Richard and Lily are confronted by police, and Jordan warns Shawn not to overuse his healing gift.
Maia sees a vision of Jordan Collier's death. Kyle's frightening blackouts are disrupting Tom's personal life. Diana is asked to hand over Maia's diary to NTAC.
Tom and Diana track down a man to a museum, and during the chase, Tom finds a mysterious lab that only he can see. Later at the office, Tom finds that all his 4400 case files are gone, and no one has ever heard of the 4400.
After living for 8 years in an alternate world that only Tom and Alana remember the world with the 4400 has returned as it was at the second the 8 years started. A 30 year old 4400 woman wakes up and finds everybody else in her local community dead. Maia puts April's love for her to a test.
A male 4400 originally from Rwanda repairs bad chromosomes of unborn. Kyle is utterly despaired as he suddenly remembers what he did during his blackout. Rishard attends a co-veteran's funeral. Diana takes s hard family decision.
NTAC is keen to find Jordan Collier's killer as Tom is desperate to find Kyle.
On John Colliers' birthday NTAC receives threatening e-mails and gets attacked by terror. Kyle is concerned that an innocent will be convicted for killing Collier. Maia gets a mysterious infection and is treated at NTAC. Isabelle has broken off her special communication with her mother and transfers it to her father. At school a girl is very interested in Kyle.
The authorities led by Dennis Hyland wants to quarantine every 4400, as several of them are sick with the same as Maia. Hunted by bad conscience Kyle somehow contacts Marsden's girlfriend.
7 of the 4400 have died and Maia gets worse all the time Out of suspicion and despair Diana threatens Dr. Hudson with a gun. Lily has run away with Isabelle and Richard pleads he to come back. Marsdem seems unable to avoid a long prison term which makes Alison contact Kyle.
A retrospective in the show in an NBC special. Narrated by Jacqueline McKenzie, "The 4400: Unlocking the Secrets" summarises the events of seasons one and two.
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.
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.
Tom and Diana continue to investigate the disappearance of the 4400 children. Isabelle and Shawn's relationship becomes public.
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.
Tom and Diana are drugged with a hallucinogen, that was created from oil that was secreted from the hands of a 4400.
Kevin Burkoff becomes a marked man when his research on promicin is discovered. When Tom and Diana search for him, they discover how far he will go to protect his work. Shawn meets his idol at the 4400 Center.
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.
NTAC and the 4400 Center work together to find Jordan Collier. Kyle Baldwin gets a surprising visitor at the state prison.
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.
Tom and Diana continue their investigation on Jordan Collier's plan for mankind. Dennis Ryland rejoins NTAC. Isabelle prepares for battle.
A high school student develops an ability after injecting promicin. Tom visits Isabelle in jail, while Diana searches for her missing sister. Following the advice of a young woman, named Cassie, Kyle is able to wake Shawn from his coma. Jordan Collier's conscience gets to him. Meanwhile, NTAC gets a new director.
Tom and Diana search for someone who has the ability to make people's worst fears come true. Danny seeks Shawn's help to find a promicin shot. Meanwhile, Cassie leads Kyle to a book that contains a prophecy about Jordan Collier.
An elderly woman develops the ability to astral project unseen by others, but she is stuck in limbo when her body is murdered, and she must find a way to contact Tom and Diana to help catch her killer. Elsewhere, Shawn decides to start healing people again despite threats.
April's new ability takes her in a danger. Meanwhile, Shawn is approached to run for public office. Kyle helps Isabelle.
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.
Jordan wants Shawn to rejoin the movement. Meanwhile, a 4400 with an amazing ability disappears.
When Jordan Collier and his followers seize control of most of Seattle, the government sends a Delta Force of enhanced soldiers to capture Collier dead or alive.
P.J. took the Promicin shot 2 months ago. Now he has an ability...
Richard returns from hiding to abduct Isabelle from Promise City, hoping to "start over." Meanwhile, Tess, her schizophrenia out of control, uses her ability to take control of a diner full of people.
Tom and Diana look for Richard, but Tom is distracted by his dreams about the future. Meanwhile, Collier is threatened by Shawn's test that could determine who would die from a Promicin shot.
Tom and Diana must race to find the source of a computer virus that could bring down Ubient software, one of the world's largest software companies that is run by suspected member of the marked, Drew Imroth. Meanwhile, Maia visits Promise City where she receives an unexpected birthday surprise: a visit from her birth parents.
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.
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.
