The interruption of arterial oxygen delivery to the myocardium during myocardial ischemia leads to a breakdown in oxidative phosphorylation and to a temporary formation of energy-rich phosphates by anaerobic glycolysis. However, the accumulation of the produced metabolites NADH, lactate and H+ rapidly blocks the key enzymes of glycolysis, so that a sufficient content of ATP necessary for cellular functions can no longer be maintained. Further accumulation of metabolic endproducts induces direct cellular damage by mitochondrial swelling and Ca2+ overload. The early contractile dysfunction can be attributed to a diminished intracellular Ca2+ release and to cellular acidosis. Furthermore, the cellular loss of K+ and anions influences the electrophysiological integrity, while the myocytic Ca2+ overload activates cellular proteases and lipases and blocks mitochondrial phosphorylation. In the later ischemic period an increased noradrenaline release from the cardiac sympathetic nerves leads to an increased adrenergic activation and promotes the occurrence of malignant arrhythmias. On the other hand, myocardial ischemia is able to induce specific, protective proteins. The transition from reversible to irreversible cellular injury is not yet clarified. There is discussion about an excessive loss of energy-rich phosphates and an accumulation of cytotoxic metabolites. The release of proteolytic enzymes and the osmotic cellular swelling may cause an irreversible damage of the cellular membrane. At this time there are several approaches to limit ischemia-induced damage. Besides the established use of beta-blockers there are some beneficial perspectives for myocardial protection by blockade of the Na(+)-H(+)-exchange or by adenosine.