The question of the existence of rational drug treatment of borderline personality disorder is discussed from two different positions. To the empiricists, the answer must rely on rigorous analysis of controlled drug trials, while to the realists theoretical conceptions of borderline personality disorder must also be seriously addressed. A rational pharmacotherapy can be claimed even when the nosological status of the disorder is not clarified but must be based on a dimensional analysis of psychopathology. Current psychotropic drugs have some but not any too impressive efficacy in the treatment of borderline personality disorder. It is argued that future drug treatment may benefit from the progress in neuroscience, especially within the area of psychobiology of personality.