The no-reflow phenomenon (NRP) is characterized by an inadequate myocardial tissue perfusion in the presence of a patent epicardial coronary artery. It generally occurs after temporary occlusion of the artery causing myocardial ischemia and necrosis that persist after relief of the vessel occlusion, without evidence of epicardial mechanical obstruction. Currently, the main scenario of NRP is the setting of percutaneous coronary interventions (PCI), especially in patients with acute myocardial infarction or saphenous vein graft disease, and its occurrence is associated with adverse clinical outcomes. Pathophysiology of NRP is not fully understood but it seems to be related with microvascular damage. Several mechanisms have been involved, such as distal microembolization, interstitial and intracellular edema, coronary spasm and capillary plugging. Diagnosis of NRP is generally based on clinical and angiographic data. Several methods have been proposed for the assessment of NRP, such as electrocardiography, myocardial contrast echocardiography, contrast- enhanced magnetic resonance imaging, nuclear imaging or positron emission tomography, that have demonstrated additional prognostic value over angiography. There are different pharmacological and mechanical approaches for the prevention of NRP but none of them have demonstrated a clear efficacy. The treatment of established NRP is mainly based on the administration of coronary vasodilators, like adenosine, verapamil or nitroprusside, but clinical results are frequently disappointing. The objective of this review is to describe the state of the art of the pathophysiology, diagnosis and pharmacological management of NRP.