Angina in the absence of obstructive coronary artery disease, sometimes referred to as cardiac syndrome X (CSX), is a debilitating condition that disproportionately affects women. More than 50% of women evaluated for angina have non-obstructive disease by cardiac catheterization, although the total numbers of women affected by CSX are unknown. Varying clinical definitions and the lack of large scale epidemiologic studies focusing on this illness have resulted in limited knowledge about its risk factors, although there appears to be an association with black race, estrogen deficiency, and insulin resistance. Contrary to prior beliefs about the benign nature of this entity, these women suffer considerable morbidity with costly economic implications that approach the lifetime costs of healthcare utilization for those with obstructive coronary disease. Two prevailing hypotheses have emerged to explain CSX: the ischemic hypothesis detailing abnormal coronary microvascular function and the non-ischemic hypothesis describing altered pain perception and myocardial hypersensitivity. Treatment strategies have focused on both of these pathways with the main goal of improving symptoms. Beta blockers provide the most convincing evidence for benefit, with other antianginals having secondary roles. Other promising pharmacologic therapies include xanthine derivatives, estrogen replacement therapy, ACE inhibitors, and statin medications, among other emerging treatment options. Neurostimulation and lifestyle factors including exercise can also be beneficial in reducing symptoms. However, managing patients with CSX can be frustrating for both patients and physicians, as there is a lack of data regarding an optimal treatment algorithm including few large-scale randomized controlled trials to clarify effective therapies.