Myocardial ischemia results in a decrease in oxygen supply to the heart, leading to cardiac dysfunction. Present therapeutic strategies for treating myocardial ischemia or infarction focus on maintaining coronary artery patency by either fibrinolysis or primary percutaneous intervention. Although these approaches have dramatically improved the prognosis in patients with angina pectoris and myocardial infarction, the complication of myocardial ischemia remains a major cause of mortality and morbidity worldwide. A novel approach that entails improving and optimizing cardiac energy metabolism of the ischemic myocardium by pharmacologically manipulating different metabolic pathways in the heart holds promise in limiting myocardial damage. Metabolic support of the ischemic myocardium is aimed at increasing glycolysis and residual oxidative phosphorylation of glucose along with decreasing fatty acid oxidation. This review discusses the various metabolic modulators, both conventional and new, along with documented evidence in both acute and chronic angina.