Women with obstructive coronary disease appear to be more challenging diagnostically and suffer a more adverse prognosis than men. More than one half of women with symptoms of ischemic heart disease have no obstructive coronary artery disease at coronary angiography, yet these women frequently have persistent symptom-related disability and consume large amounts of healthcare resources. Prior evidence has been limited regarding effective diagnostic strategies for the assessment of symptomatic women. The current report synthesizes existing evidence on diagnostic testing in women, including research from the ongoing National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. In addition to recent published evidence (drawn from much larger cohorts of women) that stress echocardiography and nuclear imaging are similar in their ability to risk-stratify women, the WISE study is exploring new pathophysiological mechanisms of microvascular dysfunction in women. An unfolding body of evidence suggests that as tests become more diagnostically and prognostically accurate, the process will become more cost efficient. The results from a growing number of large observational series and National Institutes of Health-sponsored studies are expected to be the foundation for cost-effective diagnostic and prognostic strategies for the approximately 5 million women who undergo evaluation for coronary disease annually.