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Neuroleptic malignant syndrome is a serious, life threatening complication of antipsychotic therapy with typical or atypical antipsychotics (neuroleptics). It is the rarest and the most serious of neuroleptic induced movement disorders characterized by rigidity, altered consciousness, fever and autonomic nervous system dysfunction. Two cases of neuroleptic malignant syndrome are presented. Clinical presentation, diagnostic workup, differential diagnoses, pathophysiology and treatment are discussed. Dilemmas regarding the differential diagnosis, pathogenesis, genetic predisposition and treatment of neuroleptic malignant syndrome are addressed.