The study described in the article by Potenza et al. (10) in this issue of the Journal is novel in its examination of the effects of stress and drug cue reactivity on brain function in male and female cocaine users and in comparison subjects who were social drinkers. The finding of the study, a three-way interaction of gender, drug use diagnosis, and stimulus (stress versus drug cue), shows the complexity of the relationship of brain function, gender, and drug dependence. Specifically, female cocaine users showed greater activation in a number of brain regions, including the amygdala, striatum, and insula, in response to stress cues and neutral cues. Within male cocaine users, the pattern of brain activation was similar but occurred in response to drug cues rather than stress cues. Differences between male and female cocaine users were also found in correlations between brain activation and subjective craving; female subjects showed positive correlations between subjective craving and brain activation in several brain regions, including the midbrain, hippocampus, ventrolateral prefrontal cortex, and thalamus, whereas male subjects showed positive correlations between subjective craving and activation in the insula, in the dorsolateral, dorsomedial, temporal, and parietal cortices, and in the hippocampus.