Since geeky Chuck accidentally became the mental host of the Intersect, an unprecedentedly powerful computer mind containing all information available to the US government, he's a primordial national security asset and risk. So CIA and NSA each appoint a top agent to guard Chuck, and often get involved with him in spy adventures. Meanwhile his identity must be kept secret from Chuck's sister, her perfect partner Devon, both surgeons, and Chuck's goofy colleagues in Buy More, the Burbank electronics store where he works as a cover.