Evolving knowledge regarding sex differences in coronary heart disease is emerging. Given the lower burden of obstructive coronary artery disease (CAD) and preserved systolic function in women, which contrasts with greater rates of myocardial ischemia and near-term mortality compared with men, we propose the term "ischemic heart disease" as appropriate for this discussion specific to women rather than CAD or coronary heart disease (CHD). This paradoxical difference, where women have lower rates of anatomical CAD but more symptoms, ischemia, and adverse outcomes, appears linked to abnormal coronary reactivity that includes microvascular dysfunction. Novel risk factors can improve the Framingham risk score, including inflammatory markers and reproductive hormones, as well as noninvasive imaging and functional capacity measurements. Risk for women with obstructive CAD is increased compared with men, yet women are less likely to receive guideline-indicated therapies. In the setting of non-ST-segment elevation acute myocardial infarction, interventional strategies are equally effective in biomarker-positive women and men, whereas conservative management is indicated for biomarker-negative women. For women with evidence of ischemia but no obstructive CAD, antianginal and anti-ischemic therapies can improve symptoms, endothelial function, and quality of life; however, trials evaluating impact on adverse outcomes are needed. We hypothesize that women experience more adverse outcomes compared with men because obstructive CAD remains the current focus of therapeutic strategies. Continued research is indicated to devise therapeutic regimens to improve symptom burden and reduce risk in women with ischemic heart disease.