The neuroleptic malignant syndrome and the serotonin syndrome share many clinical features and may exist on a spectrum of the same disorder. The neuroleptic malignant syndrome, however, is an idiosyncratic drug reaction, whereas the serotonin syndrome is an effect of drug toxicity. Both syndromes present with varying degrees of mental status changes and autonomic instability. In general, patients with the neuroleptic malignant syndrome have higher fevers and pronounced extrapyramidal signs with muscle rigidity, whereas patients with the serotonin syndrome have lower fevers, more gastrointestinal dysfunction, and myoclonus. Treatment for both syndromes consists of removing the offending agent and providing intensive supportive care. Syndrome-specific therapies are controversial.