Since the discovery of proven genetic mutations which predispose people to breast cancer along with the routine availability of genetic testing for such mutations, a number of issues have surfaced regarding potential methods of breast cancer diagnosis, surveillance, treatment, and risk reduction. Many of these issues pertain to the practice of radiation oncology and can affect decisions on management. This article aims to describe some of the more salient features of individuals at high genetic risk for breast developing cancer along with aspects of their tumor biology, clinical natural history, and how the radiation oncologist may address these challenges.