This article examines the effects of a fit between a person's global regulatory focus and the local task reward structure on perceptual processing and judgment. On each trial, participants were presented with one of two briefly presented stimuli and were asked to identify it. Participants were placed in a promotion focus (a situationally induced sensitivity to gains) or a prevention focus (a situationally induced sensitivity to losses) and were asked to maximize gains or minimize losses. An asymmetric payoff ratio biased the overall reward toward one identification response over the other. Two experiments tested the role of regulatory fit when internal familiarity and perceptual sensitivity were low or high. When familiarity and sensitivity were low, participants in a regulatory fit (promotion focus with gains or a prevention focus with losses) showed greater perceptual sensitivity but no response bias differences, relative to participants in a regulatory mismatch. When familiarity and sensitivity were high, participants in a regulatory fit showed a response bias toward the high-payoff stimulus but no differences in perceptual sensitivity. Speculations are offered on the neurobiological basis of this effect, as well as implications of this work for clinical disorders such as depression.