Allison DuBois (Patricia Arquette) is a strong-willed mother of three, a devoted wife, and law student who begins to suspect that she can talk to dead people, see the future in her dreams, and read people's thoughts. Fearing for her mental health, she turns for support to her husband Joe (Jake Weber), an aerospace engineer, who slowly comes to believe that what his wife is telling him just might be true, upon discovering that some of her dreams match the details of a murder in Texas.

The real challenge is convincing her boss, D.A. Devalos (Miguel Sandoval) -- and the other doubters in the criminal justice system -- that her psychic abilities can give them the upper hand when it comes to solving violent and horrifying crimes, whose mysteries often reside with those who lie beyond the grave. Information on certain people or crimes come to her in dreams or visions in cryptic forms, and never really mean what they seem to.

All of her daughters appear to have inherited their mother's gift, with Ariel (Sofia Vassilieva) and Bridgette (Maria Lark) also having visions or dreams, which usually occur when their mother is in a bind in searching for answers to her own dreams. In Season 3, Allison's youngest daughter, Marie (Madison and Miranda Carabello), is also shown to be paranormally inclined. Currently, her only ability is to watch a premium TV channel that the family does not subscribe to. Bridgette never appears to be bothered by her abilities, while Ariel usually has a harder time trying to cope with a gift she knows very little about.

Allison's younger half brother, Michael "Lucky", has the family gift too, but doesn't like to acknowledge it much, since it always seems to bring him trouble.

Allison is often accompanied by Det. Lee Scanlon (David Cubitt), who initially did not believe that she had a "gift". Allison often bends the rules of the law when she is determined to stop a crime about which she's had a vision from happening. Allison has also helped or been helped by Captain Kenneth Push of the Texas Rangers (Arliss Howard), who is the first law-enforcement person to whom Allison revealed her gift.