This paper focuses on the pharmacology, therapeutic effects and adverse effects associated with serotonin (5-HT) releasers. While some space is given to MDMA and mCPP in this paper, the review is chiefly focused on fenfluramine, dexfenfluramine and their active metabolites. After distinguishing serotonin releasers from uptake inhibitors, the authors describe how substrate-type releasers produce serotonin release. Pharmacological profiles are presented for racemic +/- fenfluramine, dexfenfluramine, mCPP and MDMA, and some of their metabolites (when known). Receptor affinities are listed for +/-fenfluramine and dexfenfluramine, but not for MDMA, which prevents a full comparison from being made between all drugs listed. Therapeutic effects listed include treatment for obesity, affective disorders, alcohol or substance consumption, seasonal affective disorder and pre-menstrual syndrome, relying on +/-fenfluramine or dexfenfluramine as models. The authors list studies that do and do not support the therapeutic potential of serotonin releasers. The subjective effects of MDMA are briefly addressed. The authors indicate that MDMA has a unique profile of effects, and state that the usefulness of serotonin releasers in treating psychiatric disorders is supported in part by findings of increased positive mood after MDMA. Surprisingly, the authors seem unaware of studies conducted by Liechti and colleagues (e.g. Liechti et al. 2000) demonstrating the importance of 5-HT release in producing the subjective effects of MDMA in humans. Primary pulmonary hypertension (PPH), valvular heart disease (VHD) and serotonergic neurotoxicity are discussed as the primary adverse events related to use of serotonin releasers. The first two conditions are primarily associated with racemic and dexfenfluramine, as well as with aminorex; no case of PPH has ever been tied to MDMA use. Action at the 5HT2B receptor is proposed as the chief cause of VHD associated with +/-fenfluramine, dexfenfluramine and other serotonergic drugs (methysergide), but not MDMA. The section examining serotonergic neurotoxicity mostly addresses the case of the fenfluramines (racemic and dexfenfluramine). The authors refer to studies they have previously conducted indicating that fenfluramine-induced functional consequences in rats. However, they also describe findings from an MRI study in obese women taking dexfenfluramine suggesting that brain dexfenfluramine levels were far below those needed to produce neurotoxicity. While seeming to accept MDMA-induced neurotoxicity as well, the authors also doubt the applicability of interspecies scaling and consider evidence for MDMA neurotoxicity inconclusive. 5-HT release itself may be responsible for neurotoxicity, but since mCPP does not produce serotonergic neurotoxicity and since central administration of MDMA into rat brain did not produce neurotoxicity, the authors favor a model of neurotoxicity based on oxidative stress. The authors are optimistic about finding a 5-HT releaser that is not neurotoxic. However, the authors are clearly far more familiar with fenfluramine than they are with MDMA, and most of their expertise relates to fenfluramine, and not to MDMA.