Most women at very high risk of breast cancer because of a mutation in the genes BRCA1 or BRCA2, or a very strong family history of breast cancer, opt for intensive breast screening rather than bilateral prophylactic mastectomy. Annual screening mammography has low sensitivity in this population in part because of the greater breast density and faster tumor growth of younger women, resulting in cancers being detected at a suboptimal stage. In 11 prospective comparative studies, the addition of annual contrast-enhanced magnetic resonance imaging (MRI) of the breast to mammography demonstrated more than 90% sensitivity, more than twice that of mammography alone. False-positive rates were higher with the addition of MRI, but specificity improved on successive rounds of screening. Although survival data are not yet available, the stage distribution of these tumors predicts a significant reduction in breast cancer mortality rate compared with that of screening without MRI. Accordingly, annual MRI plus mammography is now the standard of care for screening women aged 30 years or older who are known or likely to have inherited a strong predisposition to breast cancer (based on the above evidence) and for women who received radiation therapy to the chest before the age of 30 years (based on expert opinion). Further research is necessary to define the optimal screening schedule for different subgroups. Formal studies of other high-risk populations (eg, biopsy showing lobular neoplasia or atypical ductal hyperplasia, dense breasts, and personal history of breast cancer at a young age) should be done before MRI screening is routinely adopted for these women.