Females frequently score higher on standard tests of empathy, social sensitivity, and emotion recognition than do males. It remains to be clarified, however, whether these gender differences are associated with gender specific neural mechanisms of emotional social cognition. We investigated gender differences in an emotion attribution task using functional magnetic resonance imaging. Subjects either focused on their own emotional response to emotion expressing faces (SELF-task) or evaluated the emotional state expressed by the faces (OTHER-task). Behaviorally, females rated SELF-related emotions significantly stronger than males. Across the sexes, SELF- and OTHER-related processing of facial expressions activated a network of medial and lateral prefrontal, temporal, and parietal brain regions involved in emotional perspective taking. During SELF-related processing, females recruited the right inferior frontal cortex and superior temporal sulcus stronger than males. In contrast, there was increased neural activity in the left temporoparietal junction in males (relative to females). When performing the OTHER-task, females showed increased activation of the right inferior frontal cortex while there were no differential activations in males. The data suggest that females recruit areas containing mirror neurons to a higher degree than males during both SELF- and OTHER-related processing in empathic face-to-face interactions. This may underlie facilitated emotional “contagion” in females. Together with the observation that males differentially rely on the left temporoparietal junction (an area mediating the distinction between the SELF and OTHERS) the data suggest that females and males rely on different strategies when assessing their own emotions in response to other people.