Experiencing negative affect frequently precedes lapses in self-control for dieters, smokers, and drug addicts. Laboratory research has similarly shown that inducing negative emotional distress increases the consumption of food or drugs. One hypothesis for this finding is that emotional distress sensitizes the brain's reward system to appetitive stimuli. Using functional neuroimaging, we demonstrate that inducing negative affect in chronic dieters increases activity in brain regions representing the reward value of appetitive stimuli when viewing appetizing food cues. Thirty female chronic dieters were randomly assigned to receive either a negative (n = 15) or neutral mood induction (n = 15) immediately followed by exposure to images of appetizing foods and natural scenes during fMRI. Compared with chronic dieters in a neutral mood, those receiving a negative mood induction showed increased activity in the OFC to appetizing food images. In addition, activity to food images in the OFC and ventral striatum was correlated with individual differences in the degree to which the negative mood induction decreased participants' self-esteem. These findings suggest that distress sensitizes the brain's reward system to appetitive cues, thereby offering a mechanism for the oft-observed relationship between negative affect and disinhibited eating.