Pharmacotherapy is a very common form of treatment for borderline personality disorder or its concomitant disorders. This paper reviews all the open-label and placebo-controlled trials of second generation medications studied in samples of well-defined borderline patients. Most of the medications studied in double-blind, placebo-controlled trials were efficacious. Most of these medications were also useful in treating symptoms of affective dysregulation and impulsive aggression, which have been suggested to be the core dimensions of psychopathology of underlying borderline personality disorder. Taken together, the results of these studies suggest that the choice of medication can be guided as much by tolerability and safety as by symptom presentation. It also suggests that the common practice of polypharmacy, which has no empiric support, may be unnecessary for most patients with borderline personality disorder.