More women have died from cardiovascular disease since middle 1980's than men due to the women's older age and multiple comorbid conditions. Additionally, women with acute coronary syndrome have worse outcomes, including sudden cardiac death and death before arriving to the hospital, due to the women's atypical symptoms and the delayed diagnosis and treatment. There are many reports on the gender-specific differences in the pathophysiology of ischemic heart disease. In addition to the previous reports, the WISE study was started for improving both our understanding and the clinical outcomes of ischemic heart disease of women. These studies have suggested the structural and functional differences in the female vasculature, new paradigms for the diagnosis and treatment of the ischemic heart disease of women, the various roles of estrogen and the new therapeutic targets for preventing ischemic heart disease (IHD) or improving cardiovascular outcomes. On-going and future studies should focus on further understanding of the pathophysiology, the clinical usefulness of the new diagnostic markers that may related to the IHD of women, and the development of non-invasive, easily reproducible diagnostic tools for early detection of IHD and for predicting the adverse outcomes.