A number of studies consistently report higher rates of all clinical outcomes including postinfarction mortality, need for repeat revascularization, and reinfarction in women with cardiovascular diseases than in men. As well, the gender gap in the prevalence of cardiovascular diseases decreases progressively with increasing age. Yet, the diagnosis and treatment of these diseases differ between genders and women remain underdiagnosed for coronary heart disease. In a recent retrospective analysis we showed that, along with vessel under study and age, gender is a determinant of adenosine responses during studies of fractional flow reserve, an effect that was probably due to differences in microvascular function and that influenced the interpretation of fractional flow reserve data. These data demonstrate that not only the clinical presentation is different, but also the diagnostic approach to coronary artery disease might differ between sexes. A gap still exists in the understanding of the mechanisms, awareness, and treatment of coronary artery disease in women, but also, as we show, in the application of diagnostic modalities that are well established in men.