The degree of the damage due to ischemia depends on the delay between sudden artery occlusion and reopening. Inhibition of adenosine triphosphate (ATP) synthesis and accumulation of metabolic products due to lack of washout are the two mechanisms causing cell death. Reperfusion before all cells die does not always mean saving the cells, which are slightly injured but yet alive. Abrupt reperfusion can kill severely ischaemic but viable muscle cells. The three main harmful phenomena leading to cellular reperfusion injury are: oxidative stress, energy paradox and Inflammation. Reactive oxygen species are produced so much that the cells can manage without being damaged. The reperfusion energy scenario results in cell death by two mechanisms: one leading to broken membranes and the second resulting in new damage to the mitochondria. The reason behind the latter is the opening of the mitochondrial permeability transition pore (mPTP), which remains closed during ischaemia and opens early during reperfusion. This increases calcium overload and further contraction, and also leads to collapsing the mitochondrial membrane potential and uncoupling the respiratory chain, which may stop ATP production. Swelling of the mitochondrium causes cytochrome c release, which in turn induces the caspase cascade and promotes apoptosis. Ischaemic injury also initiates an acute inflammatory response, which is augmented by reperfusion and can contribute to the muscle damage. Reperfusion is necessary, but that "off–on" reperfusion seems to be over. Preconditioning or postconditioning (i.e., ischemia-reperfusion cycles before and after ischemia) or pharmacologic interventions can reduce the cell death due to ischemia-reperfusion injury.