Validated quantitative models are available that permit the accurate estimation of a woman's risk of developing invasive breast cancer during a specified period of time. Data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial indicate that tamoxifen can reduce the risk of developing breast cancer by at least 49% in women who are at increased risk. All premenopausal women whose 5-year risk of developing breast cancer is 1.67% or greater derive a net benefit from taking tamoxifen for risk reduction. Women who have either lobular carcinoma-in-situ or atypical ductal or lobular hyperplasia derive an even greater net benefit. Women who carry mutations in either the BRCA1 or BRCA2 gene will also experience reduced incidence of breast cancer with tamoxifen. Although postmenopausal women derive a net benefit from tamoxifen through the reduction of both breast cancer and bone fracture event rates, the risks of both invasive endometrial cancer and thromboembolic events must be balanced in older women. Physicians should identify appropriate candidates with whom to discuss the possible benefits of tamoxifen for reducing the risk of breast cancer.