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A group of 4400 people who have abducted over the last centuries mysteriously returned to Earth without aging a day.  Some of the also begin to show signs of possessing special abilities.  Agent Tom Baldwin and Diana Skouris of the National Threat Assessment Command are assigned to investigate the 4400. 

Brooke Nevin as Nikki Hudson

Nikki Hudson was the girlfriend of Danny Farrell until she slept with his brother Shawn Farrell. After Shawn became the leader of the 4400 centre she came to ask for his help in curing her father of cancer.

Chad Faust as Kyle Baldwin

Kyle Baldwin is the son of Tom Baldwin and the cousin of Shawn Farrell. One night while camping with Shawn he was been abducted by a ship but his cousin interrupted the process and was taken instead. Kyle was left in a coma until Shawn returned and healed him.

Conchita Campbell as Maia Rutledge

Maia Rutledge is the adopted daughter of Diana Skouris. In 1946 when Maria was 8 years old she was abducted. After her returned Maria was given to adoptive parents but they returned her to NTAC because they were unable to handle Maria ability to tell the future. She was taken in by NTAC agent Diana Skouris who later officially adopted her.

Jacqueline McKenzie as Diana Skouris

Diana Skouris was a NTAC agent tasked with Tom Badwin to investigate the 4400. Diana had a strong science background which around her to conclude possible scientific explanation about the 4400. Diana also became the adopted mother of the 4400 returnee child Maria Rutledge.

Joel Gretsch as Tom Baldwin

Tom Baldwin is the lead agent responsible for investigate 4400 along with his partner Diana Skouris. Tom had a personal stake in the 4400 since his son Kyle was in coma for four years while his cousin Shawn Farrell disappeared.

Kaj Erik Eriksen as Danny Farrell

Danny Farrell is the younger brother of Shawn Farrell and the nephew of Tom Baldwin. Danny resented his brother Shawn when he discovered his brother had an affair with his girlfriend. When Danny attacked his brother Shawn used his powers to defend himself. Danny was badly injured which led Shawn to leave his home and join the 4400 centre.

Laura Allen (II) as Lily Tyler

Lilly Tyler was a returnee who was abducted few years earlier. She discovered her husband has remarried and was raising their daughter with another woman. Lilly became friends with Richard Tyler who had an affair with her grandmother in the early 40ís. Lilly began a relationship with Richard and soon discovered she was pregnant with a baby girl with extraordinary powers.

Mahershalalhashbaz Ali as Richard Tyler

Richard Tyler was a solider during World War 2 fighting in the pacific war who found himself abducted and retuned to the present day. He became involved with Lily Moore despite the fact he had an affair with her grandmother Lily Bonham. He also becomes the father of Lilly child Isabelle Tyler.

Peter Coyote as Dennis Ryland

Dennis Ryland is a former NTAC director and friend of Tom Baldwin. Dennis was responsible for infecting the 4400 with an inhibitor that suppressed their abilities. When the 4400 became sick because of the inhibitor Dennis tried to cover up his crime and was willing to let the 4400 die as a result.

Samantha Ferris as Nina Jarvis

Nina Jarvis was the director of NTAC after replacing the previous director Dennis Ryland. Nina was by the book director but overtime began to respect Tom Baldwin. She was eventually replaced by Meghan Doyle.

Summer Glau as Tess Doerner

Tess Donner is a returnee who was abducted from people from the future and sent back in time. She suffers from paranoid schizophrenic and has the ability to control people.