A mysterious event causes nearly everyone on the planet to simultaneously lose consciousness for 137 seconds, during which people see what appear to be visions of their lives approximately six months in the future - a global "flashforward." A team of Los Angeles FBI agents, led by Stanford Wedeckand spearheaded by Mark Benford and his partner Demetri Noh, begin the process of determining what happened, why, and whether it will happen again. Benford contributes a unique perspective on the investigation; in his flashforward, he saw the results of six months of investigation that he had done on the flashforward event, and he and his team use those clues to recreate the investigation.

The 4400 tells the stories of 4,400 abductees after they are returned to earth. In the words of the executive producers, these are stories of people dealing with traumatic changes, driven by the mystery of what happened and why. Some of them have been affected in mysterious ways, and some will have certain abilities, both good and bad, so part of the drama will be watching them adjust to these changes within themselves. The series kicks off with a ball of light sailing toward Earth, but rather than the expected catastrophic event, thousands of returned abductees are left with no memory of their otherworldly experiences. Each has been gone anywhere from a few months to several decades but none has aged a day.