A variety of old and new substances and drugs with powerful psychotropic effects have come into common use during the past decade. Patterns of involvement include experimental, occasional, regular controlled, and regular uncontrolled use, with physical and psychologic dependence and toxic reactions as the frequent result of abuse patterns. This increase in drug use has affected all sectors of the medical profession, with physicians more likely to see patients who use and misuse various psychotropic substances. We discuss the diagnosis and management of common acute problems related to substance use, intoxication, overdose, and withdrawal. The drugs and substances discussed include the opiates, barbiturates (and other sedative hypnotic agents including alcohol and benzodiazepines), cocaine and the amphetamines, phencyclidine, hallucinogens, inhalents, and marijuana.