Myocardial ischemia-reperfusion (I-R) injury is the major event contributing to the morbidity and mortality associated with coronary artery disease. Although several factors contribute to I-R-mediated myocardial injury, compelling evidence indicates that generation of radicals and other reactive oxygen species are important mediators of this type of cardiac damage. Importantly, endurance exercise has been shown to provide significant cardioprotection against an I-R insult. This tutorial lecture will discuss the mechanism(s) responsible for exercise-mediated cardioprotection. In particular, recent experiments investigating the role of heat shock proteins in exercise-induced cardioprotection will be highlighted. Further, the role that endogenous antioxidants play in exercise-induced cardioprotection will also be discussed. Finally, future directions for cardioprotection research will be explored.