Reactive oxygen species are a ubiquitous danger for aerobic organisms. This risk is especially elevated in legume root nodules due to the strongly reducing conditions, the high rates of respiration, the tendency of leghemoglobin to autoxidize, the abundance of nonprotein Fe and the presence of several redox proteins that leak electrons to O2. Consequently, nodules are particularly rich in both quantity and diversity of antioxidant defenses. These include enzymes such as superoxide dismutase (EC 18.104.22.168) and ascorbate peroxidase (EC 22.214.171.124) and metabolites such as ascorbate and thiol tripeptides. Nodule antioxidants have been the subject of intensive molecular, biochemical and functional studies that are reviewed here. The emerging theme is that antioxidants are especially critical for the protection and optimal functioning of N2 fixation. We hypothesize that this protection occurs at least at two levels: the O2 diffusion barrier in the nodule parenchyma (inner cortex) and the infected cells in the central zone.