Borderline personality disorder (BPD) is a severe mental disorder with a multifactorial etiology. The development and maintenance of BPD is sustained by diverse neurobiological factors that contribute to the disorder's complex clinical phenotype. These factors may be identified using a range of techniques to probe alterations in brain systems that underlie BPD. We systematically searched the scientific literature for empirical studies on the neurobiology of BPD, identifying 146 articles in three broad research areas: neuroendocrinology and biological specimens; structural neuroimaging; and functional neuroimaging. We consolidate the results of these studies and provide an integrative model that attempts to incorporate the heterogeneous findings. The model specifies interactions among endogenous stress hormones, neurometabolism, and brain structures and circuits involved in emotion and cognition. The role of the amygdala in BPD is expanded to consider its functions in coordinating the brain's dynamic evaluation of the relevance of emotional stimuli in the context of an individual's goals and motivations. Future directions for neurobiological research on BPD are discussed, including implications for the Research Domain Criteria framework, accelerating genetics research by incorporating endophenotypes and gene x environment interactions, and exploring novel applications of neuroscience findings to treatment research.