The clinical triad of fever, movement disorder, and altered mentation known as NMS represents an infrequent yet highly lethal side effect of neuroleptic therapy. Although awareness and recognition are on the rise, underdiagnosis of the disorder may represent a neglected clinical problem of major proportions considering the number of patients treated with neuroleptics. The recognition of problems such as NMS and tardive dyskinesia point out the need for investigation of low-dose efficacy and neuroleptic serum levels. The idea that neuroleptics are free of severe side effects has created a clinical fallacy that high doses of high potency neuroleptics should be administered to acutely psychotic patients and that low doses of neuroleptics may be used for various diagnostic entities. The emphasis on NMS and its 20% mortality rate should point out that neuroleptics should only be used when clinically indicated to treat psychosis and should be given in the lowest possible dose that achieves antipsychotic effects. Although treatment strategies are still being formulated, aggressive medical care and specific drug therapies exist to reverse the symptoms of this syndrome. With proper education, psychiatrists and other specialists can recognize and treat NMS effectively and thus prevent its malignant outcome.