Chemoprevention with tamoxifen and oophorectomy are thought to be effective in decreasing the incidence of breast cancer in women at increased risk for the disease. There is mounting data supporting the idea that hormonal interventions that reduce estrogen exposure to breast epithelium, such as prophylactic oophorectomy and tamoxifen, are effective in breast cancer prevention in both BRCA1 and BRCA2 mutations carriers. Several recent studies directly address the protective effect of tamoxifen and oophorectomy in BRCA mutation carriers and suggest that these endocrine manipulations decrease the risk of primary and secondary breast cancers. Ongoing studies aim to better define the effect of tamoxifen in these very high-risk women and determining whether factors, such as earlier age of use or prior prophylactic oophorectomy, impact tamoxifen's effect. Based on existing data, we recommend that women with deleterious mutations in BRCA1 or BRCA2 be informed of the beneficial effect of oophorectomy on breast cancer risk and that women who choose breast cancer screening instead of prophylactic mastectomy be offered tamoxifen as a prevention option.