Theories of empathy suggest that an accurate understanding of another’s emotions should depend on affective, motor, and/or higher cognitive brain regions, but until recently no experimental method has been available to directly test these possibilities. Here, we present a functional imaging paradigm that allowed us to address this issue. We found that empathically accurate, as compared with inaccurate, judgments depended on (i) structures within the human mirror neuron system thought to be involved in shared sensorimotor representations, and (ii) regions implicated in mental state attribution, the superior temporal sulcus and medial prefrontal cortex. These data demostrate that activity in these 2 sets of brain regions tracks with the accuracy of attributions made about another’s internal emotional state. Taken together, these results provide both an experimental approach and theoretical insights for studying empathy and its dysfunction.