This review explores the recent experience with, and the basis for, the use of selective estrogen receptor modulators to treat and prevent breast cancer. As new agents are unveiled, they will continue to be tested against tamoxifen. A number of new selective estrogen receptor modulators are in clinical development in an attempt to decrease the unwanted effects of tamoxifen. Raloxifene holds the promise of treating osteoporosis with the beneficial side effect of breast cancer prevention. Additionally, two different classes of hormonal agents, the aromatase inhibitors and estrogen receptor down-regulators, which have no estrogen-like properties at any site, appear to be promising new treatments for advanced breast cancer.