The purpose of this review is to evaluate the comparative effectiveness of tamoxifen citrate, raloxifene, and tibolone to reduce risk for primary breast cancer, assess the nature and magnitude of harms, and examine how benefits and harms vary by age, breast cancer risk status, and other factors. In addition, it examines issues related to clinical effectiveness, such as patient choice, concordance, adherence, and persistence of use, and evaluates methods to appropriately select patients for medication therapy to reduce risk of breast cancer.