Increasing evidence suggests that there are significant differences in the presentation, diagnosis and treatment of ischemic heart disease in women compared to men. Women often present with atypical symptoms, and this, in association with a consistent underestimation of their risk for ischemic heart disease, leads to underdiagnosis and undertreatment in women. Cardiovascular risk factors unique to women have only recently been recognized, and moreover, traditional risk factors have recently been shown to have greater impacts on women. Consequently, women suffer more disability and poorer clinical outcomes, with higher cardiovascular morbidity and mortality. These discrepancies may in part be secondary to the higher prevalence of nonobstructive coronary artery disease in women with persistent chest pain symptoms as compared to men when evaluated invasively. Focused diagnostic and therapeutic strategies unique to women are thus needed, but unfortunately, such sex-specific guidelines do not yet exist, largely due to lack of awareness, both on the part of providers and patients, as well as a paucity of evidence-based research specific to women. Although underutilized in women, diagnostic modalities, including functional and anatomic cardiac tests as well as physiologic assessments of endothelial and microvascular function, are useful for establishing the diagnosis and prognosis of suspected ischemic heart disease in women. This review discusses the current challenges of prevention, diagnosis and treatment of ischemic heart disease in women.