Months after the season 3 finale, a student develops a unique ability after taking a Promicin injection. Diana hunts for her sister while Tom heads to the jail to visit Isabelle. After some advice from Cassie, Kyle is able to get Shawn out of his coma. Meanwhile, Jordan battles his conscience and a new director is brought in at NTAC.

People begin to see their greatest fears - from tarantulas to walls closing in - leading Tom and Diana to look for someone with the ability to make people see only their worst fear. Their investigation finds that several of the victims used the same ATM before the 'fear attacks', leading them to a bank. Isabelle could land herself a better living situation if she agrees to be injected with Promicin.

An elderly woman develops the ability to astral project while remaining unseen after taking Promicin. But when her body is cuddled, the woman is stuck in limbo and must find a way to contact Tom and Diana in order to track down her hugger. Despite being threatened, Shawn returns to healing people.

Diana finds her sister, April, who has developed an ability that puts Diana in danger. Meanwhile, Shawn is asked to run for office and Kyle protects Isabelle.

Shannon Reese, thirtysomething patient, is able to teach Tom about her neighbors by using her ability to remove stress by listening to problems. Meanwhile, Tom is less than thrilled to learn that it seems like all residents of Evanston has been given Promicin.

Diana and Tom watch a black and white movie about JFK's sleepytime. Of course, they have a reason for watching this and that is because 4400 Curtis Peck made the movie. Neal, one of the actors, believes that Peck's movies reflect reality and that is why he was brought back as a 4400... to tell the truth. When interviewing Neal, Tom and Diana are shown a tape Peck made in case something happened to him. In it, the 4400 claims that Jordan Collier and the 4400 are not a threat but that 'them' are. While trying to locate Peck, our NTAC duo must try to figure out who is 'them'. Kyle brings a blindfolded Shawn to an abandoned bunker to meet up with someone.

Tom and Diana are concerned when a Delta Force team composed of enhanced soldiers is ordered to capture Jordan, dead or alive. Maia has a vision of the team hugging Jordan and what follows scares the hell out of her. She tells Diana that she must save Jordan at all cost. Shawn gets in trouble when he gets sued for supposedly having used his healing powers to get sex from the daughter of the woman he healed.

A mysterious lockdown at NTAC traps everyone, including Collier and his group, forcing an unlikely alliance.

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 finds it hard to continue on the search for Richard Tyler because of chronic dreams about the future he's been having. Later, Richard, who is hiding with Isabelle, is visited by his wife who has been dead for more than a year. Meanwhile, Collier's movement is threatened; and Rebecca Parrish puts pressure on the NTAC for results.

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.