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.
Jack and Henderson wage an assault on the submarine as Bierko prepares to launch an attack against L.A. Chloe brings in someone from her past to aid her. Martha and Aaron enlist Mike’s help in their plans to expose Logan.
Jack takes his fight directly to the President as he attempts to force a confession from him that will prove his involvement in the day’s events. Martha vents her hatred for her husband in front of the press as Logan gives a eulogy over Palmer’s body. Jack and Audrey share a tender moment when it seems the crisis has subsided, but Jack finds that his problems have only begun as his past catches up with him.
As the escape continues, lives are lost and Pope and Bellick do everything in their power to capture the convicts.
Ted tries to keep Robin from going on a camping trip so that she can spend time with him. Barney enlists the help of an old flame to perform a rain dance. At the same time Marshall finds out about Lily’s interview for the fellowship in San Francisco.
Bierko escapes from the transport taking him to Division and uses his last canister of nerve gas for a surprise strike. Jack is forced to work with Henderson to find Bierko, but Henderson wants something in return. Logan takes drastic steps to deal with Aaron when he won’t go along with the cover-up.