A large percentage of patients, predominantly female, who undergo coronary angiography for typical chest pain do not have significant coronary stenosis. Many of these patients with microvascular myocardial disease have left ventricular hypertrophy, cardiomyopathies, valve disease, or other clinical conditions. The definition of microvascular angina is based on (i) symptoms of myocardial ischemia, (ii) absence of obstructive coronary artery disease (<50% stenosis on coronary angiography or coronary computed tomography scan), (iii) objective evidence of myocardial ischemia (ischemic electrocardiographic abnormalities during episodes of chest pain and/or myocardial perfusion defects or regional contractility abnormalities), and (iv) pathological indices of microcirculation (index of microcirculatory resistance >25, coronary flow reserve <2.0) and/or microvascular spasm (TIMI flow <2) during intracoronary vasoreactivity tests. The basic mechanisms and the diagnostic tests of microvascular dysfunction are reported in detail.From a clinical standpoint, while the crucial role of microcirculation in determining short- and long-term prognosis is evident, efforts to date to improve clinical outcomes in patients with microvascular obstruction have had limited success, most likely because microvascular dysfunction is a multifactorial process with several interdependent underlying pathophysiological mechanisms. Therefore, further studies are needed to develop effective therapeutic strategies for microvascular myocardial disease.