Microvascular coronary dysfunction (MCD) is an increasingly recognized cause of cardiac ischemia and angina that is diagnosed more commonly in women. Patients with MCD present with the triad of persistent chest pain, ischemic changes on stress testing, and no obstructive coronary artery disease on cardiac catheterization. Data from the National Heart, Lung, and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation (WISE) study show that the diagnosis of MCD is not benign, with a 2.5% annual risk of adverse cardiac events including myocardial infarction, stroke, congestive heart failure, and death. The gold standard diagnostic test for MCD is the invasive coronary reactivity test (CRT), which uses acetylcholine, adenosine, and nitroglycerin to test endothelial-dependent and -independent microvascular and macrovascular coronary function. The CRT allows for diagnostic and treatment options as well as further risk stratification of patients for future cardiovascular events. Treatment of angina and MCD should be aimed at ischemia disease management to reduce the risk of adverse cardiac events, ameliorate symptoms to improve quality of life, and decrease morbidity from unnecessary and repeated cardiac catheterization in patients with open coronary arteries. A comprehensive treatment approach aimed at risk factor management, including lifestyle counseling regarding smoking cessation, nutrition, and physical activity, should be initiated. Current pharmacotherapy for MCD may include treatment of microvascular endothelial dysfunction (with statins, angiotensin-converting enzyme inhibitors, or low-dose aspirin), as well as treatment for angina and myocardial ischemia (with β-blockers, calcium channel blockers, nitrates, or ranolazine). Additional symptom management techniques may include tricyclic medication, enhanced external counterpulsation, hypnosis, and spinal cord stimulation. Although our current therapies are effective in treating angina and MCD, large randomized outcome trials are needed to optimize strategies to improve morbidity and mortality.