This review is focused on aggressive behavior in adult patients with major mental disorders. Aggression, agitation, and hostility are defined. The roles of intramuscular forms of ziprasidone and olanzapine in the treatment of acute agitation and aggression are discussed. We review general considerations pertaining to persistent aggression in inpatients and outpatients, including comorbidity of major mental disorders with substance use disorders and personality disorders. The role of clozapine as an antiaggressive agent is well established, particularly in inpatients. Evidence also exists for the efficacy of risperidone, olanzapine, quetiapine, and aripiprazole. Anticonvulsants and lithium are widely used with the intent to control aggression, but their efficacy lacks strong evidential support. Benzodiazepines have a role in controlling acute agitation, but their long-term use for persistent aggression is not recommended. There is evidence for antiaggressive effects of SSRIs and hormonal agents with antiandrogenic properties. Beta-adrenergic blockers and electroconvulstive treatment are rarely used in clinical practice to control aggression, but they may be effective. The heterogeneity of aggressive behavior is a challenge for developing rational treatments. Emerging genetic findings hold a promise of future treatments of aggressive behavior developed on the basis of individual patients' genotypes.