Breast cancer is the most commonly diagnosed invasive malignancy and the second leading cause of cancer death in women. This chapter considers epidemiologic evidence regarding the association between physical activity and breast cancer risk from 73 studies conducted around the world. Across these studies there was a 25% average risk reduction amongst physically active women as compared to the least active women. The associations were strongest for recreational activity, for activity sustained over the lifetime or done after menopause, and for activity that is of moderate to vigorous intensity and performed regularly. There is also some evidence for a stronger effect of physical activity amongst postmenopausal women, women who are normal weight, have no family history of breast cancer, and are parous. It is likely that physical activity is associated with decreased breast cancer risk via multiple interrelated biologic pathways that may involve adiposity, sex hormones, insulin resistance, adipokines, and chronic inflammation. Future research should include prospective observational epidemiologic studies relating proposed biomarkers to breast cancer risk and also randomized controlled trials to examine how physical activity influences the proposed biomarkers. Exercise trials will provide more clarity regarding the appropriate type, dose, and timing of activity that relate to breast cancer risk reduction.