Because they share one pathognomonic sign (major hyperthermia), classic or environmental heatstroke and malignant hyperthermia have often been confronted from the therapeutic point of view. As expected and according to major physiopathological discrepancies between both syndromes, analysis of published data does not support effectiveness of dantrolene in heatstroke despite its significant reduction in mortality in malignant hyperthermia. If cooling methods still represent the cornerstone of the heatstroke therapeutic approach, the magnitude of heat-related deaths and the morbidity associated with the August 2003 French heatwave have highlighted the need for more ambitious methods of treatment.