Exertional heat stroke is usually experienced as a result of a prolonged and intensive exercise. It is a life-threatening condition that is characterized by an increase in core body temperature and rhabdomyolysis. The associated hyperkalemia and metabolic acidosis may lead to an acute renal, cardiac, and hemostatic failure. Exactly, the same symptoms are noticed in case of the anesthesia-induced malignant hyperthermia (MH), an inherited disorder of the skeletal muscle ryanodine receptor. This receptor is a Ca(2+) channel that is activated by the volatile anesthetic agents and depolarizing muscle relaxant. The presence of MH-associated ryanodine receptor variant in the individuals who suffered from EH and improvement of the symptoms with dantrolene has frequently raised the question as to whether the two disorders actually represent one and the same disease. Nevertheless, an exact explanation of the susceptibility of the genetically predisposed MH individuals to ER remains elusive. We have attempted to review the published clinical reports to explore the possibility that ER and EH represent one and the same disorder.