In this paper we report our experience with 24 cases in which there was a homicide or homicides committed in association with use of large amounts of psychoactive drugs. Many, if not most of these homicides, would not have occurred without drug effects, for frequently there was evidence of grossly illogical thinking in close temporal association with use of intoxicants and in many cases there was no previous history of violence, no evidence of premeditation, no plan to avoid arrest and little or no discernible motivation. Usually there were multiple losses or other severe stress in the lives of the persons committing the homicide in the months preceding the crime. The stress increase was accompanied by increased and extraordinary intake of psychoactive substances. We theorize that high doses of psychoactive drugs impaired severely the brain systems upon which the mental functions of reality testing and judgment depend. Drug induced impairment of reality testing and judgment is frequently uncritically equated with hallucinations, disorientation, changes in time perception or other drug induced mental phenomena. Impairment of reality testing and judgment are basic criteria for linking drug effects with the behavior of homicide in the cases reviewed.