Lethal catatonia and neuroleptic malignant syndrome are both rare and life-threatening problems. The clinical presentations are very similar, with striking features of altered mental status, fevers, and muscle rigidity.Lethal catatonia is a neuropsychiatric disorder that was first described in the early 1800s, 100 yrs before the use of neuroleptics and other antipsychotic agents. Presently, it appears that this disorder may be an extension and terminal event of excited catatonia. Modern psychopharmacologic practice has almost eliminated this lethal progression. This syndrome is most commonly associated with underlying psychiatric pathology, but may rarely be associated with organic disease. Severe hyperthermia is one of the most striking changes that occurs with lethal catatonia along with a wide spectrum of abnormal behavior, including severe lability of mood, anorexia, bizarre behavior, hallucinations, mutism, catatonia, and muscle rigidity. Hyperthermia may culminate in death secondary to dehydration, end-organ failure, and cardiovascular collapse if it is unrecognized or refractory to therapy. Therapy consists of aggressive supportive therapy, antipsychotic agents, and, on occasion, electroconvulsive therapy (1).The neuroleptic malignant syndrome is an uncommon, but severe, adverse reaction to antipsychotic and neuroleptic medications. Neuroleptic malignant syndrome is characterized by high fever, muscle rigidity, autonomic dysfunction, and an alteration in the level of consciousness. Patients frequently have increased WBC counts and serum creatinine phosphokinase (CPK) concentrations. Neuroleptic malignant syndrome is reported to have a mortality rate of approximately 20%. The syndrome is a diagnosis of exclusion and must be differentiated from lethal catatonia, infectious etiologies, central nervous system pathology, malignant hyperthermia, toxic encephalopathy, hyperthyroidism, tetany, parkinsonism, and drug overdose or toxin ingestion (2–5).We present a patient who developed lethal catatonia, which was initially, successfully treated with an antipsychotic drug. However, the patient subsequently developed neuroleptic malignant syndrome. The diagnostic dilemma and therapeutic challenges of this clinical situation are reviewed.