Trust and cooperation are essential features of human interpersonal transactions. Recent evidence suggests that these processes are related to brain areas implicated in social decision-making. These novel data provide a unique opportunity to characterize psychopathological conditions in which trust and cooperation are potentially impaired. Using economic games, independent investigations revealed that trust and cooperation are disrupted in patients with borderline personality disorder who have severe difficulties in their personal relationships and exhibit abnormal emotion regulation. Data from functional neuroimaging indicated that the abnormal activation of the anterior insula might be a key factor during these processes, together with the cingulate cortex and the amygdala.