Tamoxifen (Nolvadex) has been in use for over 20 years and currently is probably the most prescribed anti-cancer medication in the world. It is an orally effective, synthetic, non-steroidal, estrogen antagonist and agonist agent. In studies and trials it has been shown to have only limited side effects. It has produced regressions in women with fibrocystic changes, including precancerous ones, and in those with metastatic breast cancer, where its benefits were first observed. It has increased disease free survival (DFS) and overall survival (OS) rates when given as an adjuvant systemic type of therapy in women with early breast cancers, and it has reduced the incidence of contralateral breast cancers. In addition there are reports indicating its long term use, especially in postmenopausal women, may produce overall health benefits. Over the years an increasing body of data has emerged allowing for viable hypotheses about the possible use of tamoxifen in the prophylaxis of breast cancer, namely that when administered in long-term therapy it may reduce the incidence of breast cancer in women so treated, that it may provide overall health benefits, particularly in postmenopausal women, and that its benefits should far outweigh any risks from its relatively limited side effects. However, carefully designed and conducted clinical trials are needed to test the safety of tamoxifen and its ability to prevent breast cancer before it is advocated for the prophylactic treatment of healthy women to prevent breast cancer, even realizing the increasing magnitude of the breast cancer problem.