Studies on natural long-term course of borderline personality disorder (BPD) as well as on treatment outcome suggest that social integration remains seriously unsatisfactory in the majority of the subjects concerned. Identification of typical borderline problems in social interaction should facilitate both, treatment development and elucidation of the related neuropsychological mechanisms and underpinnings. This review focuses on the experimental investigation of three core domains of social interaction: social affiliation, cooperation and hostility. Data converge, that patients meeting criteria for BPD show a tendency to misinterpret neutral situations, feel socially rejected during normative inclusion conditions and reveal difficulties in repairing cooperation after experiencing disappointment. While from a clinical perspective, most attention has been focused on relationships of BPD patients with their significant others, the literature suggests that encounters with unknown individuals also indicate impairments in interaction behavior, and that such impairments can be linked to altered cerebral processing. Considering these findings psychosocial treatments should extend the programs and develop trainings in normative behavior.