Aggression among patients with serious mental illness occurs relatively infrequently, but it is a significant concern for patients, relatives, mental health professionals, and the public. Recognition of this risk and providing access and continuity of appropriate psychiatric care should be major clinical and administrative objectives in the management of violence in psychotic patients. To date, pharmacologic approaches have been unclear and inconsistent. At present, typical antipsychotics continue to have a primary role in acute management and in long-term management, in which noncompliance necessitates the use of long-acting depot neuroleptic preparations. Atypical antipsychotics in acute and long-acting intramuscular forms doubtless will influence and expand the choice for acute management of hostile psychotic patients and the long-term management of poorly compliant patients who are at risk to become violent on relapse. Persistent aggression should be managed by atypical antipsychotics with a preferential indication for clozapine, for which the most data on efficacy are available. The role of adjunctive medications is presently unclear. A major focus of care should be to refine legal processes and to conduct intervention studies aimed at enhancing treatment compliance. Violence risk reduction is not only crucial from a societal perspective, but also it is a humanitarian necessity to alleviate the burden and stigma for patients with serious mental illness.