Originally, the biosocial model of borderline personality disorder (BPD) was based on clinical experience and intuition. Within the last 30 years, tremendous progress has been made strengthening the empirical basis for this model. Currently, most researchers postulate three core domains of BPD psychopathology: affective dysregulation, interpersonal disturbances, and problems in identity. Whereas affective dysregulation research has the strongest empirical support, morphological and functional neuroimaging findings point to alterations of the central regions of the emotion regulation circuitry: prefrontal cortex, amygdala, hippocampus, and insula. It is unclear whether these alterations are due to early adverse childhood experience or instead are more genetically driven, resulting in a pattern of emotional hypersensitivity,. However, evidence shows that successful DBT changes dysfunctional emotions and cognitive patterns as well as related neurobiological underpinnings. This chapter discusses the current state of research on the biological underpinnings of BPD.