Early revascularization of the infarct-related artery by primary percutaneous coronary intervention (PPCI) has become the gold standard therapy in ST-segment elevation myocardial infarction (STEMI). However, in a number of patient undergoing PPCI, epicardial coronary artery reperfusion: does not translate into myocardial reperfusion: a phenomenon called as no-reflow. The no-reflow phenomenon has a multifactorial pathogenesis, including: distal embolization, ischemia-reperfusion injury, and individual predisposition of coronary microcirculation to injury. Angiographic and electrocardiographic indexes may be used for the diagnosis. Also, lack of ST-segment elevation resolution is considered an established marker of no-reflow. Importantly, the no-reflow phenomenon provides prognostic information in STEMI patients because it is associated with low ventricular ejection fraction, adverse left ventricular remodelling and mortality at follow-up. Various mechanical devices and pharmacological approaches have been proposed to prevent and to treat the phenomenon: the assessment of mechanisms of no-reflow might guide the development of personalized form of treatment. This paper will be focused on the postulated mechanisms of the phenomenon, modalities for the diagnosis, and the main treatment options.