An early distinction between the early and reversible changes of cellular ischemia and the irreversible changes of cell necrosis is essential to a rational program for the treatment of coronary artery disease, to a definition of the permissible limits of nonperfusion of the anoxic arrested heart at open-heart surgery, and to a determination of the maximal allowable transport time for cardiac transplantation. The factors in the myocardial cellular environment that support cellular viability and help maintain homeostasis are reviewed. Reversible surgically induced anoxic arrest is contrasted with the irreversible arrest and cell necrosis which often attend the myocardial anoxia of coronary occlusion. The enhancement of glycolysis, other changes in carbohydrate metabolism, and the depressed oxidation and lipid storage associated with alterations in lipid metabolism are outlined and their interrelationships discussed. The effect of the myocardial tissue acidosis which accompanies ischemic metabolism is an important factor in determining the reversibility of the effects of ischemia. The probable role of myocardial acid hydrolases in pathological ischemic autolysis is described. A sequence of cellular events induced by ischemia and leading to ultimate cell death is outlined. Promising areas for future investigation into the pathogenesis of myocardial infarction and into improved methods of treatment are suggested.