Selective estrogen receptor modulators are a growing class of nonsteroidal compounds with estrogen-like actions in bone, lipid metabolism, and antiestrogenic actions in the breast. Tamoxifen and its derivatives have a weak estrogenic action in the uterus and are responsible for endometrial hyperplasia. Raloxifene does not stimulate endometrial growth but is less effective than tamoxifen for the treatment of patients with breast cancer. The duality of selective estrogen receptor modulators and 1 7B-estradiol actions is explained by several hypotheses referring to the molecular biology of estrogen receptor. Clinical trials are conducted with raloxifene in post-menopausal women. The results show a significant decrease in vertebral fracture risk and a decrease of low-density lipoprotein cholesterol, with no change in triglyceride levels. Endometrial thickness does not change. Interestingly, the risk for newly diagnosed breast cancer decreases significantly with no change in risk for estrogen receptor-negative tumors. Selective estrogen receptor modulators might change the way we manage hormone replacement therapy of postmenopausal women.