OBJECTIVE This review familiarizes clinicians with the symptoms of overdose and withdrawal, as well as neurologic complications, associated with particular illicit drugs. RESULTS Recent arrivals on the recreational drug scene include synthetic cathinone analogs, synthetic cannabinoid agonists, and a variety of novel hallucinogens. CONCLUSIONS Clinicians need to be aware of neurologic disorders associated with particular illicit drugs and should consider drug abuse in any patient with unexplained symptoms and signs.In addition to tobacco and alcohol, a large number of substances, legal and illegal, are used recreationally. Broad categories include opioids, psychostimulants, marijuana and related agents, sedatives, hallucinogens, inhalants, phencyclidine and related agents, and anticholinergics. Each type of agent has its own characteristic symptoms of overdose and withdrawal, and many agents are associated with trauma, infection, seizures, stroke, cognitive impairment, and teratogenicity. Some drugs have unique neurologic complications not encountered with other agents. A history of recreational drug use should be sought in any neurologic patient regardless of age or socioeconomic status.