After Sheila bumps into Johnny’s ex-wife, Angie, Tommy seeks her out. Jerry and Rose spend a very romantic evening together, while Mrs. Turbody is in jail for statutory rape. This gives Tommy some relief but also new worries, and Franco loses his daughter, Keela.
A teenager is found disoriented in the middle of traffic and taken to a detention facility. Later, Nicole Trager, a psychologist, comes to examine him, and takes him home. He gets on the bad side of both Trager kids, Josh and Lori, and annoys Stephen, Nicole’s husband. But one by one, Kyle influences them to accept him.
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.
The crew decide to save some children from a disabled school bus as they go to call in Harlem. However, the soon meet up with an upset Rev. Al Sharpton. Franco finally realizes why Alicia is so interested in him. Mike and his roommate discuss their sexuality. Sean ends up telling Tommy about his feelings for Maggie. Sheila has a proposal for Tommy. Janet wants to talk to him about their settlement, but with no lawyers involved.
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.
Franco begins to fear he’s becoming Alicia’s boy toy, while Tommy finds a way to end the fling between Damien and his science teacher. The rest of the crew also face their own problems – Lou is becoming real unstable emotionally, the chief has financial problems, and Sean is afraid of Tommy finding out who he’s been sleeping with.
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.
During a night out, Franco and Tommy meet two women. Tommy is finding himself bribing his daughter Colleen before she tells their mother about his indulgent treatment of her sister Katy. Jerry visits his wife Jeannie in her expensive nursing home and soon goes to Lou for financial help. Meanwhile John Sr. insists on having his 83rd birthday at a restaurant that no one else likes.
Janet decides to meet with Tommy after not speaking with him for months since the sudden death of their son. Uncle Teddy refuses to allow anyone to help him get out prison. Tommy is shocked when he accidentally discovers just who his nephew has been sleeping with.