Despite the reduction of mortality secondary to cardiovascular diseases observed in the last decades, ischemic heart disease remains the most common cause of death worldwide. Among the spectrum of ischemic heart disease, myocardial infarction accounts for most deaths. Since the introduction of the coronary care units in the 1960s, and until the latest antithrombotic drugs, myocardial infarction survival improved by 40-50%. However long-term mortality after myocardial infarction has not improved as short-term mortality. Moreover, the decline of mortality has apparently reached a "plateau" in the past 15 years. In this review we describe the steps of the improvement in ischemic heart disease mortality, from the bed rest to the possible future of treating microcirculation. In fact, coronary artery disease is not only a disease of large vessels that can be visualized with coronary angiography. The small network of pre-arterioles and arterioles that supply the myocardium can be also affected in ischemic heart disease. Thus, despite the introduction of effective recanalization strategies for epicardial coronary arteries such as thrombolysis and, more recently, primary percutaneous intervention, some patients may not achieve effective myocardial reperfusion due to microvascular dysfunction or damage after myocardial myocardial infarction. This phenomenon is named no reflow. We believe that no reflow, through the incomplete reperfusion that can account for a higher rate of adverse event in the follow up, should be regarded as one of the open issues in the modern treatment of myocardial infarction.