Myocardial preservation is crucial for the success of cardiac surgery and for minimizing postoperative myocardial dysfunction. The use of cardiopulmonary bypass (CPB) introduces significant risk of myocardial injury, particularly during the ischemic interval caused by aortic cross-clamping and the subsequent reperfusion phase. Early cardiac surgeries were often limited by postoperative myocardial failure, despite technically successful operations, due to inadequate myocardial protection. The evolution of cardiac surgery has thus been closely tied to advances in myocardial preservation techniques. The introduction of aortic cross-clamping, while enhancing surgical access, interrupted myocardial perfusion and highlighted the need for protective strategies. These include cardioplegia, left ventricular venting, and hypothermia—all aimed at reducing myocardial oxygen demand and safeguarding the heart during periods of ischemia. Contemporary approaches focus not only on protection during cross-clamping but also on optimizing myocardial function during reperfusion and weaning from CPB. This chapter explores the development and refinement of these strategies, addresses the unique challenges of operating on a beating heart, and underscores the importance of balancing oxygen supply and demand to ensure optimal recovery of cardiac function.