Rapid interventional restoration of coronary blood flow is the most effective therapy to limit infarct size in today}s cardiology. The early phase of reperfusion represents, however, a window of therapeutic opportunities largely unused in the clinic. Experimentally it has been clearly shown that the modalities of reperfusion have a substantial impact on infarct size, since reperfusion itself can damage the myocardium (reperfusion injury). The major cause for acute injury of the cardiomyocytes in reperfusion is their hypercontracture. Cytosolic Ca (2+) overload and malfunction of cell organelles, i. e. sarcoplasmic reticulum and mitochondria, determine the pathophysiology of reperfusion injury. The underlying mechanisms can be influenced in the first minutes of reperfusion by activation of protective signalling pathways (reperfusion therapy). First clinical studies confirm the efficacy of acute reperfusion therapy.