Psychopathy is a disorder of high public concern because it predicts violence and offense recidivism. Recent brain imaging studies suggest abnormal brain activity underlying psychopathic behavior. No reliable pattern of altered neural activity has been disclosed so far. This study sought to identify consistent changes of brain activity in psychopaths and to investigate whether these could explain known psychopathology. First, we used activation likelihood estimation (p < 0.05, corrected) to meta-analyze brain activation changes associated with psychopathy across 28 functional magnetic resonance imaging studies reporting 753 foci from 155 experiments. Second, we characterized the ensuing regions functionally by employing metadata of a large-scale neuroimaging database (p < 0.05, corrected). Psychopathy was consistently associated with decreased brain activity in the right laterobasal amygdala, the dorsomedial prefrontal cortex, and bilaterally in the lateral prefrontal cortex. A robust increase of activity was observed in the fronto-insular cortex on both hemispheres. Data-driven functional characterization revealed associations with semantic language processing (left lateral prefrontal and fronto-insular cortex), action execution and pain processing (right lateral prefrontal and left fronto-insular), social cognition (dorsomedial prefrontal cortex), and emotional as well as cognitive reward processing (right amygdala and fronto-insular cortex). Aberrant brain activity related to psychopathy is located in prefrontal, insular, and limbic regions. Physiological mental functions fulfilled by these brain regions correspond to disturbed behavioral patterns pathognomonic for psychopathy. Hence, aberrant brain activity may not just be an epiphenomenon of psychopathy but directly related to the psychopathology of this disorder.