Borderline personality disorder is characterized by affective instability, impulsivity, identity diffusion, and interpersonal dysfunction. Perceived rejection and loss often serve as triggers to impulsive, suicidal, and self-injurious behavior, affective reactivity, and angry outbursts, suggesting that the attachment and affiliative system may be implicated in the disorder. Neuropeptides, including the opioids, oxytocin, and vasopressin, serve a crucial role in the regulation of affiliative behaviors and thus may be altered in borderline personality disorder. While clinical data are limited, the authors propose alternative neuropeptide models of borderline personality disorder and review relevant preclinical research supporting the role of altered neuropeptide function in this disorder in the hope of stimulating more basic research and the development of new treatment approaches.