Remarkable strides have been made in perioperative myocardial protection for heart operations. Recent advances in understanding the physiology of myocardial ischemia and its protective responses suggest that there is a possibility for further improvement. Some of these strategies are discussed in this article, which updates current thinking in regard to operative developments contributing to myocardial protection, preconditioning, inhibition of adenosine triphosphate catabolism, the critical role of adenosine, management of myocardial edema, antioxidant therapy, endothelial cell injury, and the interaction between activated leukocytes and the endothelium. Some potential new directions for cardioprotection are identified.