Neuroleptic malignant syndrome is a disease that, in addition to being rare, is potentially life-threatening. Its early diagnosis by differentiation from other diseases, also rare, and thus unknown by much of the medical personnel, such as lethal catatonia and malignant hyperthermia, where the pathophysiological mechanism is totally different but just as devastating and potentially life-threatening.In this review, special relevance will be made to its epidemiology, pathophysiology, differential diagnosis, and therapeutic approach.Emphasis will be placed on the importance of maintaining a high suspicion of this clinical picture, taking into account that there is a current actual increase in the formulation of neuroleptic drugs and emergence of psychiatric illness in our population. Maintaining a high suspicion of this clinical picture will allow early diagnosis and initiate timely and appropriate treatment, and thus reducing the associated mortality and morbidity.