Ecstasy is the second most widely abused illegal drug in Europe. Ecstasy is the colloquial name for 3,4-methylenedioxymethamphetamine (MDMA), but not all Ecstasy tablets contain MDMA. When taken in hot, crowded environments, Ecstasy/MDMA users have developed acute complications that have had fatal consequences. Epidemiological evidence indicates that adverse reactions to Ecstasy/MDMA intoxication are rare and idiosyncratic. Potential mechanisms of action are reviewed. In animal studies, MDMA damages serotonergic fibres and reduces the number of serotonin transporter sites within the CNS. Demonstration of neurotoxicity in human users of Ecstasy is hampered by a number of confounds that the majority of published studies have failed to address. These confounds are reviewed and their impact is discussed.