Women who inherit a BRCA mutation face a high lifetime risk of developing breast cancer. Given the high penetrance of these mutations, prevention is of extreme importance. Here, we review the literature regarding the role of body size and of physical activity in the context of BRCA-associated breast cancer. There is some evidence to support a protective role of a healthy body size and of regular physical activity among mutation carriers, particularly during adolescence or early adulthood. Factors which increase the physiologic expression of the normal copy of the BRCA1 or BRCA2 gene and thereby normalize protein levels, contribute to stem cell homeostasis, and/or affect hormone levels, might mitigate the effects of an inherited BRCA mutation. Preliminary evidence from one in vivo study and from one epidemiologic report suggests that an increase in BRCA1 mRNA expression occurs with increasing levels of physical activity. The prospect of changing lifestyle for the purpose of preventing breast cancer in high-risk women, complemented by mechanistic evidence, warrants evaluation in large-scale prospective studies.