The prevalence of psychopathology among children and adults with mental retardation is several times higher than the prevalence within the general population. Accordingly, psychopharmacologic interventions often play an important role in treatment programming for those with mental retardation and comorbid affective and behavioral disturbances. Medications that are of benefit include the stimulant medications for attention-deficit hyperactivity disorders; lithium for cyclic mood disturbances and explosive, aggressive behavior; and the neuroleptics for psychotic disorders, self-injury, and stereotypic behavior. Other potentially efficacious medications include the serotonin reuptake blockers, the opioid antagonists, and the beta-adrenergic blocking agents. Clinical treatment will be greatly enhanced as systematic investigations increase in number and methodologic rigor.