An increasingly large proportion of women with unilateral breast cancer are treated with bilateral mastectomy. The rationale behind bilateral surgery is to prevent a second primary breast cancer and thereby to avoid the resultant therapy and eliminate the risk of death from contralateral breast cancer. Bilateral mastectomy has been proposed to benefit women at high risk of contralateral cancer, such as carriers of BRCA1 and BRCA2 mutations, but for women without such mutations, the decision to remove the contralateral breast is controversial. It is important to evaluate the risk of contralateral breast cancer on an individual basis, and to tailor surgical treatment accordingly. On average, the annual risk of contralateral breast cancer is approximately 0.5%, but increases to 3% in carriers of a BRCA1 or BRCA2 mutation. Risk factors for contralateral breast cancer include a young age at first diagnosis of breast cancer and a family history of breast cancer. Contralateral mastectomy has not been proven to reduce mortality from breast cancer, but the benefit of such surgery is not expected to become apparent until the second decade after treatment. An alternative to contralateral mastectomy is adjuvant hormonal therapy (such as tamoxifen), but the extent of risk reduction is smaller (approximately 50%) compared to 95% or more for contralateral mastectomy. This Review focuses on the risk factors for contralateral breast cancer, and discusses the evidence that bilateral mastectomy might reduce mortality in patients with unilateral breast cancer.