The endogenous opioid peptides and their receptors play important roles in Pavlovian fear conditioning in many species, including mice, rats, and humans. These roles are best viewed as regulating the conditions for fear learning by determining the actions of predictive error on association formation. Evidence will be reviewed showing such roles for opioid receptors in ventrolateral quadrant of the midbrain periaqueductal gray (vlPAG). These roles are shared across mammalian species because many of the effects of opioid receptor manipulations on fear learning first reported in rodents have now been documented in humans.