The primary goal in reopening an infarct-related artery is the restoration of myocardial tissue-level perfusion. In a variable proportion of patients with ST-elevation myocardial infarction, however, microcirculatory impairment may persist after epicardial coronary artery recanalization. This phenomenon is known as microvascular obstruction (MVO). Ischemic injury, reperfusion injury, and distal embolization along with the individual response to each of these mechanisms are variably involved in the pathogenesis of MVO in the single patient. Importantly, MVO is associated with a worse prognosis both at short- and long-term follow-up. MVO can be assessed in the cath-lab by simple angiographic indexes, such as Thrombolysis in Myocardial Infarction grade score and Myocardial Blush Grade, or by invasive measures of coronary flow pattern. Imaging techniques, such as myocardial contrast echocardiography or cardiac magnetic resonance, and ST-segment resolution on standard electrocardiogram are used in the days following reperfusion with the patient in the coronary care unit. In this article, we review the available data regarding pathogenesis, diagnosis and the prognostic significance of MVO after primary percurtaneous coronary intervention in ST-elevation myocardial infarction patients, with a brief highlighting on the crucial role of its prevention and its early detection.