Cardiovascular disease remains the number one cause of mortality for women in the United States, with coronary artery disease (CAD) accounting for 54% of all cardiovascular deaths. CAD claims the lives of more than 250,000 women each year and is therefore the single largest killer of American women. For several decades, the under-representation of women in clinical trials led to both a lack of available sex-specific evidence and a generalized misconception that CAD was a "man's disease." In actuality, not only are women vulnerable to CAD, they typically develop it 10 to 15 years later than men. Furthermore, sex differences exist in the mortality rates of women and men with CAD, such that once CAD is present in women, they have worse outcomes than their male counterparts. Consequently, early and accurate diagnosis of CAD is crucial for reducing mortality rates in women. Stress myocardial perfusion imaging (MPI) using contemporary techniques has been shown to have significant value in the diagnosis and prognosis of CAD in women. In the risk assessment of women with an intermediate clinical pretest likelihood of CAD, using MPI with exercise or pharmacologic stress has been shown to add incremental value to clinical variables or exercise electrocardiogram stress testing alone. This review discusses the clinical role of stress MPI in the management of women with suspected CAD.