The no-reflow phenomenon (NRP) is defined as the lack of adequate myocardial tissue perfusion despite a patent epicardial coronary artery. The incidence of NRP varies between 2-5% of elective percutaneous coronary interventions (PCI) and 30% in primary PCI. Clinically, it is an independent predictor of myocardial infarction, in-hospital mortality, and long-term mortality. It may be categorized in interventional (after PCI, especially in saphenous venous grafts) or reperfusion NRP (after re-opening of a totally occluded coronary artery, usually during primary PCI or thrombolysis). There are many physiopathological factors implicated: distal microembolization, interstitial and intracellular edema, coronary spasm and capillary plugging. Although reperfusion and no reflow is a field of intense research, no single mechanical or pharmacological therapy has demonstrated a clear efficacy against NRP, probably due to its multifactorial nature. Once established, the treatment of NRP is based on vasodilators like adenosine, verapamil, nitroprusside or nicorandil. However, the efficacy of these measures is poor, so every effort should be made to prevent the apparition of NRP. The objective of this report is to provide an update of the pharmacological armamentarium available for the prevention and treatment of NRP, and suggest a systematic approach of the management of NRP according to the different possible clinical scenarios.