Over the last century at least 4,400 who were overlooked, undervalued or otherwise marginalized vanished from the planet without a trace. One night, they were all inexplicably returned in an instant to Detroit, having not aged a day and with no memory of what happened to them. As the government races to understand the phenomenon, analyze the potential threat and contain the story, an empathetic social worker and a hardened community corrections officer, are among the civil servants called upon to deal with the uncanny refugees.

As the 4400 become even more disenchanted with their accommodations, new rules have everyone on edge. Andre and LaDonna help Claudette push her new-found ability to new limits. Keisha and Jharrell explore a way to ease the tension for a small group of the returned and Shanice gets an unexpected visitor. Rev begins to believe he may be part of a higher calling.

LaDonna signs up for fifteen more minutes of fame but quickly realizes she doesn't have the clout she once had, so she turns to an unlikely source to help further her agenda. Jharrell picks an inopportune time to speak his truth. Andre is eager to get back to medicine while everyone is eager to feel a bit of normalcy again. Shanice takes a step towards repairing her relationship with her daughter. Hayden and Mildred enjoy an impromptu celebration.

There is finally some good news for a few of the 4400. Andre looks to study some of his new friends but mistakes from his past begin to affect him in present day. Rev learns some information about his son.

Keisha hears the truth about the day she lost her sister, moving her to take a chance. Shanice and Andre enjoy a day out. Hayden and Mariah grow closer.

Jharrel and Keisha must earn the trust of the 4400 if they truly want to help keep them safe. Hayden convinces LaDonna and Andre to visit Ypsi Med. Rev continues to grow his flock.

Claudette begins to assert her independence. Rev keeps his flock close, further raising Jharrel's suspicions. LaDonna considers her next move. Keisha has a date with Jessica. Andre is concerned by his latest discovery.

Logan's adjustment to Shanice's return has been harder than he let on, meanwhile, Rev is beginning to see the light. Mildred lets her emotions get the better of her, possibly endangering the rest of the 4400.

The scene is chaotic, and everyone is still reeling after Mildred’s on camera performance, meanwhile the government tries to figure out their next move. Rev is confused by his new ability, Jharrel get some unexpected news, and no one seems to know Ladonna’s whereabouts.

With everyone at the Bois Blanc still on edge, the government deals another blow to the 4400. Meanwhile, Jharrel gets some shocking information about his brother, Shanice and Andre continue to grow closer, and Mildred resurfaces.

While Shanice helps to prepare the Bois Blanc for a celebration, others are preparing for war. LaDonna returns to the hotel and we learn what she has experienced out in the real world and what she knows about the 44orum. After a disturbing incident, Hayden realizes the comfort of Kaminsky home may not be what is safest for everyone. Jharrell reunites with his brother but is Manny to be trusted and what is his connection to Claudette? Meanwhile, an unfortunate misunderstanding might prove fatal for one of the 4400.

Logan is the only witness to a savage crime, that, to all others does not seem to exist, meanwhile Claudette stands up to a group of anti-4400's. Mildred rallies the troops when she fears Milicent might be in trouble and we get a glimpse into the sisters' lives growing up and the mysterious Caleb.

Tensions rise as an attack is made on the Bois Blanc, putting everyone’s life in danger. Shanice and Logan do their best to keep Hayden safe, while Claudette and Jharrell try to reason with Manny. Meanwhile, Mildred still believes her sister can be saved and LaDonna takes to the streets in an effort to end the threat against the 4400.