Neuroleptic malignant syndrome (NMS) continues to be an unpredictable and rare, but potentially fatal complication of antipsychotic medications. Presumptively linked to dopamine blockade, it nonetheless occurs in patients receiving newer atypical antipsychotics. The features of NMS, its pathophysiology, differential diagnosis, clinical course, risk factors, and morbidity and mortality are reviewed. Nonpharmacologic management centers on aggressive supportive care including vigilant nursing, physical therapy, cooling, rehydration, anticoagulation. Pharmacologic interventions include immediate discontinuation of antipsychotics, judicious use of anticholinergics, and adjunctive benzodiazepines. The utility of specific agents in actively treating NMS is reviewed. Bromocriptine and other dopaminergic drugs and dantrolene sodium have alternatively been considered without merit or efficacious. Guidelines for using these agents are presented. Electroconvulsive therapy, also somewhat controversial, is identified as a second line of treatment. Finally, management of the post-NMS patient is also reviewed.