4400 centers on the return of 4400 people who, previously presumed dead or reported missing, reappear on Earth. Though they have not aged physically, some of them seem to have deeper alterations ranging from superhuman strength to an unexplained healing touch. A government agency is formed to track the 4400 people after one of them commits a murder.
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.
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.
Diana locates her sister, April, who took promicin and developed an ability that puts her life in jeopardy.
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.
Jordan Collier's movement takes a huge step forward when his followers settle in the heart of Seattle.
Tom, Diana, Jordan, Shawn, Kyle, Isabelle, Maia, Meghan, Marco, PJ and Brady all wake up inside NTAC without any memory of how they got there.
Richard surprises Isabelle when he shows up in Promise City but the happy reunion takes a turn when Richard kidnaps her in hopes to start a new life with his daughter.
Tom has trouble focusing on the hunt for Richard Tyler because of dreams he's having about the future.
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.