Early reperfusion during evolving myocardial infarction is essential for saving myocardium and patients' lives. Nevertheless, lethal reperfusion injury can occur, limiting myocardial salvage. Numerous experimental studies have proved the deleterious effects of reoxygenating endothelial cells and cardiomyocytes. The major breakthrough was the proof that the success of myocardial reperfusion can be modified by preconditioning and, more recently, by postconditioning, a form of progressive and interrupted reperfusion. Three theories have been put forward to explain reperfusion injury: (1) oxidative stress resulting in a burst of oxygen-radical formation, which can cause membrane damage; (2) the energy paradox, which suggests that restarting energetic mitochondrial machinery results in myofibrillar hypercontracture, cytoskeleton fragility and membrane rupture; and (3) the role of inflammation, which addresses the effects of leucocyte accumulation and activation. Fortunately, reperfusion injury salvage kinases can be up-regulated and in some circumstances may block, in a manner similar to pre- or postconditioning, the diabolical cycle leading to necrosis and/or apoptosis of viable cells. The end effectors of the survival system are two mitochondrial channels - the mK-ATP channel and the mitochondrial permeability transition pore. Better understanding of these salutary molecular mechanisms and their triggers may result in a new era of reperfusion techniques.