The treatment and follow-up strategies of acute ST- elevation myocardial infarction (STEMI) have improved in the last decades, but incidence of both death and disability after myocardial infarction is still high. Rapid re-establishment of blood flow to the infarct related artery (IRA) is recommended treatment of choices. Paradoxically, the reperfusion of the blood to the ischemic myocardium may result in extensive myocardial cell death at the time of reperfusion called ischemia-reperfusion (I/R) injury. Pathophysiological mechanisms of the (I/R) injury are not fully understood but oxidative stress, intracellular calcium overload, intracellular acidosis, inflammation and metabolic disturbances seems to contribute to the I/R injury.Animal studies have shown that various interventions directed at mediators of I/R injury may reduce size of the total infarction. Application of the same principles in clinical studies on patients with acute myocardial infarction, however have generally been neutral. Conditioning the heart by short repetitive cycles of reperfusion and reocclusion of IRA has shown beneficial on infarct size both in animal models and small pilot studies. Postconditioning the heart of the STEMI patients at the time of reperfusion has shown controversial results, regarding infarct size and left ventricular remodelling, indicates that there may be several factors influencing the reperfusion injury mechanism.Targeting novel intracellular signalling mechanisms of I/R injury in STEMI by pharmacological or ischemic postconditioning has shown some promising results, which have to be confirmed. Further evaluation of the effect of postconditioning in larger groups of STEMI patients is needed. If a reduction of final infarct size can be unequivocally shown by this procedure, larger studies with clinical endpoints may be warranted.