4400 overlooked, undervalued, or otherwise marginalized people who vanished without a trace over the last hundred years are all returned in an instant, having not aged a day and with no memory of what happened to them. As the government races to analyze the potential threat and contain the story, the 4400 themselves must grapple with the fact that they've been returned with a few "upgrades", and the increasing likelihood that they were all brought back now for a specific reason.

As various members of the Frank family come together for a college graduation party in Chicago, they find their bonds being tested -- and strengthened -- in surprising ways.