The pharmacotherapy of personality disorders is less developed than are psychological treatments in this area, but they are a logical prolongation of psychobiological models of personality and temperament, and respond to the need of many clinicians in front of difficult patients. The assessment of drugs effects in personality disorders includes some important conceptual and methodological issues. Categorical or dimensional instruments evaluating baseline personality and under-treatment changes are now available. Such studies are necessary of long duration, with difficult patients, and use specific outcome criteria. The results obtained in the field of pharmacotherapy of personality disorders can be classified according to DSM IV axis-II categorization. In anxious personalities (cluster C), some isolated studies suggest a favourable effect of antidepressants on obsessive-compulsive dimension, on avoidant personality disorder, and on inhibition and trait-anxiety, especially when serotoninergic agents are used. Few studies have been conducted in cluster A personality disorders, and some are in favour of the interest of low doses of antipsychotic drugs in this group. Most studies have been conducted in cluster B, and especially in antisocial and borderline personality disorders. Partial positive results have been obtained using various classes of drugs for dealing with aggression and impulsive behaviors, including lithium, beta-blockers, carbamazepine, valproate, antipsychotic drugs, and also SSRIs. Self-harm and suicidal behaviors seem to be partially but significantly improved by antidepressants and low doses of antipsychotics. Opioid antagonisms may be helpful for these indications in the future. Other symptom-oriented strategies for psychopharmacology have been conceptualized, focused on depressive personality, emotional lability, cognitive and perceptual disturbances, or interpersonal sensitivity. Overall, the pharmacotherapy of personality disorder remains to date one of the less explored in psychiatry research. Nevertheless, it may lead in the future to the development of effective treatments, in complement to psychotherapy, for actually severe, chronic, and disabling disorder.