The rapid restoration of coronary flow to the jeopardized myocardium has become an essential part of therapy after acute myocardial infarction. Despite an open infarct-related artery, breakdown of or obstruction to coronary microvasculature can markedly reduce blood flow to the infarct zone. This effect is known as the no-reflow phenomenon. Advances in imaging modalities have improved visualization of no reflow, showing its frequency to be higher than was estimated by clinical judgment alone. This phenomenon is important because it correlates with infarct size and provides useful prognostic information. No reflow is associated with reduced left ventricular ejection fraction, left ventricular remodeling, and poor clinical outcomes, placing patients with this effect in a high-risk group among reperfused patients. The focus of reperfusion therapy is shifting towards improved myocardial perfusion, which could promote functional recovery of viable muscle, reduce infarct expansion, and increase the delivery of blood-borne components, thereby accelerating the healing process. Various pharmacologic interventions and catheter-based devices to retrieve embolic materials have been proposed. Further studies to improve understanding of the pathophysiology of microvascular dysfunction will, however, help in the further development of preventive and therapeutic strategies. In this article, I discuss in depth the data available on the no-reflow phenomenon.