Two recent trials of the efficacy of hormone therapy (HT) have challenged our understanding of the influence of menopause and the alleged protective role of estrogen against atherosclerotic cardiovascular disease.1,2 Let us consider the background of evidence that necessitated these landmark studies to better interpret their unexpected findings. In the United States and Europe cardiovascular disease (CVD) is the leading cause of death in women as well as men. In women participating in the Framingham Study, the lifetime risk of developing coronary heart disease (CHD) is 32%, a risk 3 times that of breast cancer, which women fear more.3