The prospects for making a vast impact on the morbidity and mortality from breast cancer lie more likely in the area of chemoprevention. Tamoxifen was the first agent considered in a preventive setting. Different studies analyzed the role of tamoxifen in prevention and, although the first results were apparently contradictory, they showed notable reductions in breast cancer. In the same period, in the MORE trial, raloxifene unexpectedly produced a larger reduction of breast cancer than was seen for tamoxifen. This result led to other chemoprevention studies to establish the role of raloxifene. Particularly, the STAR trial showed that raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer and has a lower risk of adverse event. At the same time, the third-generation aromatase inhibitors (AIs) have shown good efficacy in advanced breast cancer and a low toxicity profile. They offer another approach to prevention, which may be superior or complimentary to the use of Selective Estrogen Receptor Modifiers (SERMs). Currently no AIs have yet been fully evaluated. New studies comparing the different agents together are needed and further follow up of the existing chemoprevention trials are necessary to determine which women will truly benefit from this kind of prophylaxis.