Cardiovascular disease is the leading cause of death in women. Although overall mortality from coronary heart disease (CHD) has decreased, there are subsets of patients, particularly young women, in whom the mortality rate has increased. Underlying sex differences in CHD may be an explanation. Women have more frequent symptoms, more ischemia, and higher mortality than men, but less obstructive coronary artery disease (CAD). Despite this, traditional risk factor assessment has been ineffective in risk stratifying women, prompting the emergence of novel markers and prediction scores to identify a population at risk. Sex differences in manifestations and the pathophysiology of CHD also have led to differences in the selection of diagnostic testing and treatment options for women, having profound effects on outcomes. The frequent finding of nonobstructive CAD in women with ischemia suggests microvascular dysfunction as an underlying cause; therefore, coronary reactivity and endothelial function testing may add to diagnostic accuracy in female patients. In spite of evidence that women benefit from the same therapies as men, they continue to receive less-aggressive therapy, which is reflected in higher healthcare resource utilization and adverse outcomes. More sex-specific research is needed in the area of symptomatic nonobstructive CAD to define the optimal therapeutic approach.