Reperfusion therapy decreases myocardium damage during an acute coronary event and consequently mortality. However, there are unmet needs in the treatment of acute myocardial infarction, consequently mortality and heart failure continue to occur in about 10% and 20% of cases, respectively. Different strategies could improve reperfusion. These strategies, like generation of warning sign recognition and being initially assisted and transferred by an emergency service, could reduce the time to reperfusion. If the first electrocardiogram is performed en route, it can be transmitted and interpreted in a timely manner by a specialist at the receiving center, bypassing community hospitals without percutaneous coronary intervention capabilities. To administer thrombolytic therapy during transport to the catheterization laboratory could reduce time to reperfusion in cases with expected prolonged transport time to a percutaneous coronary intervention center or to a center without primary percutaneous coronary intervention capabilities with additional expected delay, known as pharmaco-invasive strategy. Myocardial reperfusion is known to produce damage and cell death, which defines the reperfusion injury. Lack of resolution of ST segment is used as a marker of reperfusion failure. In patients without ST segment resolution, mortality triples. It is important to note that, until recently, reperfusion injury and no-reflow were interpreted as a single entity and we should differentiate them as different entities; whereas no-reflow is the failure to obtain tissue flow, reperfusion injury is actually the damage produced by achieving flow. Therefore, treatment of no-reflow is obtained by tissue flow, whereas in reperfusion injury the treatment objective is protection of susceptible myocardium from reperfusion injury. Numerous trials for the treatment of reperfusion injury have been unsuccessful. Newer hypotheses such as " ", in which the interventional cardiologist assumes not only the treatment of the culprit vessel but also the way to reperfuse the myocardium at risk, could reduce reperfusion injury.