Several large, prospective trials have evaluated tamoxifen compared with placebo for breast cancer risk reduction in women at increased risk of breast cancer. Combined results from these trials demonstrate that tamoxifen at 20 mg/d reduced the incidence of breast cancer by 38%. The risk of developing breast cancer is the primary determinant of net benefit, with greater benefits accrued to women with the highest risk of breast cancer. Age and the presence of risk factors for increased toxicity also have an effect on the net benefit associated with tamoxifen. The greatest clinical benefit from tamoxifen is evident for younger women who are at lower risk of thromboembolic complications and uterine cancer, women without a uterus, and women with breast biopsy results indicative of atypical hyperplasia or lobular carcinoma in situ. Raloxifene has also been shown to reduce the risk of invasive breast cancer in women with osteoporosis and is as effective as tamoxifen for reducing the risk of invasive breast cancer in postmenopausal women at increased risk of breast cancer. In high-risk younger, postmenopausal women, raloxifene seems to offer a net benefit when comparing the reduction of risk of breast cancer and prevention of fractures with the risk of stroke, venous thromboembolic events, uterine events, and symptomatic side effects. Raloxifene offers an acceptable option for breast cancer risk reduction in postmenopausal women.