Four randomized prospective trials have evaluated tamoxifen for chemoprevention of breast cancer. The National Surgical Adjuvant Breast and Bowel Project P-1 trial reported that tamoxifen reduced the risk of invasive breast cancer by 49%. Two smaller European trials, the Royal Marsden Hospital Chemoprevention Trial and the Italian Tamoxifen Prevention Study, demonstrated no decrease in the incidence of breast cancer among women using tamoxifen. The International Breast Cancer Intervention Study confirmed that tamoxifen can reduce the risk of breast cancer in healthy women. The Multiple Outcomes of Raloxifene Evaluation trial, which evaluated the use of raloxifene (Evista) to prevent osteoporosis, found that the risk of invasive breast cancer decreased by 76%. A uniform theme in these trials is that tamoxifen reduces the risk of breast cancer among women at high risk for the disease. Tamoxifen is currently approved for breast cancer risk reduction. However, because of the side effects associated with its use (i.e., endometrial cancer and thromboembolism), other agents are being investigated. The Study of Tamoxifen and Raloxifene is designed to compare the efficacy of tamoxifen and raloxifene in reducing breast cancer risk. Aromatase inhibitors will also be studied in the setting of chemoprevention for breast cancer.