The current status of pharmacological treatments of self-injurious behavior (SIB) and aggression in persons with mental retardation and autism was reviewed in the literature. Much of the existing literature is derived from anecdotal clinical experience, with a relative lack of well-controlled studies to determine the efficacy of different treatments. Although all psychotropics have been used to manage SIB and aggression, particularly promising are the data on the use of opioid antagonists like naltrexone. Beta-blockers may also have some role, but more controlled, systematic studies are needed. Use of neuroleptics is on the decline because of their adverse effects, such as tardive dyskinesia and possible impairment of cognitive functions. We assert that the behavioral problems of SIB and aggression are at times manifestations of different psychiatric syndromes. They present in a modified, atypical form in the developmentally disabled population because of cognitive limitations. Further understanding and classification of the psychopathology associated with this behavior is essential for its successful treatment.