The recreational drug "ecstasy" (3,4-methylenedioxymethamphetamine, or MDMA) is widely used by young people throughout the world. Experimental studies indicate that MDMA damages serotonergic neurons in animals and possibly in humans. Repeated use may induce long-term neurotoxic effects, with cognitive and behavioral implications. We reviewed both the preclinical and the clinical literature to assess the evidence for persistent neuropsychiatric sequelae in humans. We focused on studies of chronic recreational use and reports of presence or absence of neurological, psychiatric, and psychological problems related to MDMA exposure. These investigations show repeated use of ecstasy to be associated with sleep, mood, and anxiety disturbances, elevated impulsiveness, memory deficits, and attention problems, which may persist for up to 2 years after cessation. In a subset of humans, particularly adolescents, depletion of serotonin by MDMA use may hasten or enhance vulnerability to a wide array of neuropsychiatric problems. Together, the studies reviewed provide substantial evidence that MDMA causes neuronal damage in animals and humans. Additional research is necessary to determine whether the MDMA-induced destruction of serotonergic neurons can have long-term and possibly permanent neuropsychiatric consequences in humans.