Prior whole-body hyperthermia is able to protect the myocardium against ischaemia-reperfusion injury by reducing cellular necrosis, preserving the ventricular function and preventing the occurrence of arrhythmias. These cardioprotective effects are associated with reduction of oxidative stress, preservation of the high-energy phosphate levels and synthesis of heat stress proteins. A better understanding of this powerful protective adaptation of the myocytes would be of interest for potential clinical application, and rational design of specific agents that activate this mechanism will hopefully follow soon.