For patients with acute myocardial infarction (MI), the immediate therapeutic goal is to establish the patency of the infarct-related artery. Prolonged myocardial ischemia, however, often breaks down the coronary microvasculature, and the flow to the infarct myocardium may be markedly reduced. This is called the no-reflow phenomenon. This phenomenon is important not solely because it correlates with infarct size but because it provides additional prognostic information. With recent advances in imaging modalities, the no-reflow phenomenon is observed more frequently than when clinical judgment alone is used. Patients with this phenomenon are associated with poor functional and clinical outcomes. Now, the no-reflow phenomenon can be a parameter with which to predict high-risk patients. The focus of reperfusion therapy has shifted toward the improvement of myocardial perfusion. The improvement of myocardial perfusion could promote the functional recovery of viable muscle and reduce infarct expansion, which is associated with favorable clinical outcomes. For this purpose, pharmacological interventions and catheter-based devices to retrieve embolic materials have been proposed. Advances in our understanding of the pathophysiology of microvascular dysfunction would aid the development of therapeutic strategies for its prevention and treatment.