3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a known neurotoxin in animals. This review discusses the history, pattern of use, pharmacology, acute and long-term effects of MDMA. Emphasis is given to the concern that MDMA may induce long-term cognitive and psychiatric effects. MDMA is an illegal substance, and investigations of the effects of exposure in human beings have limitations and weaknesses. There are numerous studies suggesting a correlation between MDMA exposure and psychopathology, and that the psychotropic effects may be long-lasting or permanent. However, it is not possible to conclude that there is a causal relationship between exposure and the increased psychopathology observed in MDMA users. Longitudinal studies are needed to assess whether MDMA causes persistent cognitive impairment and/or psychiatric symptoms in human beings.In animal models, the illegal substance of abuse 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been shown to confer serotonergic neurotoxicity. Whether this also applies to human beings is a subject of controversy. If applicable, MDMA exposure should be expected to induce symptoms of serotonergic hypofunction, such as depression, psychoses, anxiety states and impaired cognition.This review attempts to summarize the current knowledge regarding the effects of MDMA in human beings, with emphasis on long-term neuropsychiatric effects. Relevant literature was obtained through searches in the database PubMed and reference lists in seminal articles published prior to 2007. The following search terms were used: MDMA + human + psychiatry, MDMA + human + depression, and MDMA + human + review. The searches identified approximately 1500 articles that were subjected to screening.