This article will focus on the results of the Women's Health Initiative on the effects of hormone replacement therapy on coronary heart disease, stroke, venous thromboembolism, breast cancer, and colorectal cancer. Data from other relevant trials, including the most recent data on ovarian and uterine cancer risk and on gynecologic cancer patients, are also discussed to provide some guidelines on prescribing hormone replacement therapy in clinical practice, particularly in gynecologic cancer survivors.