The introduction of neuroleptics in the 1950’s was a turning point in psychiatric treatment. The new drugs brought hope to millions of patients and their doctors. However, there were also some side-effects, one of which is Neuroleptic malignant syndrome (NMS), a rare complication of antipsychotic treatment and untreated it may lead to mortality as high as 20%. The incidence of NMS, estimated to be 0.01–0.02%, has decreased significantly probably due to higher awareness of the diseases and shift to atypical antipsychotics. The aim of this study was to present the signs and symptoms of this rare condition and describe management possibilities since this condition is observed not only in psychiatric departments but also in emergency rooms. NMS is thought to be related to change caused by neuroleptics within the central nervous system due to dopamine D2 receptor antagonism, especially nigrostriatal pathways and the hypothalamus. There are three symptoms which are considered as major and indicate a high probability of NMS: muscle rigidity, hyperthermia (core body temperature above 38.5 °C), and elevated creatine phosphokinase concentration (above 1000 U/l). NMS is a diagnosis of exclusion and clinicians must be vigilant in detecting early signs of NMS. The basic management in NMS is antipsychotic discontinuation and proper supportive care of the patient (vital signs monitoring, hydration, correction of electrolyte and acid-base disturbances). In more severe cases, the introduction of bromocriptine or dantrolene, as well as benzodiazepines, may indicated. Further usage of neuroleptic in patients with a history of NMS should be with care, and low doses of low-potency neuroleptics or atypical neuroleptics seem to be the best treatment choice.