Physical exercise has been found to decrease the risk of breast cancer by undefined means. In our prior communication, we proposed lipid peroxidation to be a relevant mechanism for breast cancer protection associated with many established protective factors such as parity, oophorectomy, menopause, physical exercise, etc. [Gago-Dominguez M, Castelao J, Pike MC, Sevanian A, Haile RW. Role of lipid peroxidation in the epidemiology and prevention of breast cancer. Cancer Epidemiol Biomark Prevent 2005;14:2829-39]. In the present communication, we examine in detail the physical exercise-breast cancer relationship in light of the lipid peroxidation mechanism. We provide additional supporting evidence for the hypothesis that oxidative stress-induced apoptosis may be a mechanism responsible, at least in part, for the protective effect of exercise in breast cancer. Specifically, we describe (1) the sources of free radicals occurring during exercise, (2) existing experimental data on physical exercise, lipid peroxidation and cancer, (3) existing supporting data implicating exercise-induced reactive oxygen species (ROS) as the mechanism responsible for increased apoptosis in different cell systems, and (4) changes in the antioxidant enzymes glutathione S transferases (GSTs), superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) that occur after physical exercise, which are believed to be a physiologic response to oxidative stress induced by physical exercise.