Breast cancer is the most commonly diagnosed invasive malignancy and the second leading cause of cancer death in women globally. This review considers epidemiologic evidence regarding the association between physical activity and breast cancer risk. Across these studies there was a 25% average risk reduction among 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 among 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 are related to breast cancer risk reduction.Breast cancer remains a leading cause of cancer incidence and mortality in most developed countries worldwide. While significant international research has examined risk factors for breast cancer, most identified risk factors are nonmodifiable. During the past 20 years, over 90 studies have been conducted worldwide that have examined some aspects of the association between physical activity and breast cancer risk reduction. The purpose of this chapter is to review both the epidemiologic evidence and hypothesized biologic mechanisms whereby physical activity may influence breast cancer risk.