The redox-active metal manganese plays a key role in cellular adaptation to oxidative stress. As a cofactor for manganese superoxide dismutase or through formation of non-proteinaceous manganese antioxidants, this metal can combat oxidative damage without deleterious side effects of Fenton chemistry. In either case, the antioxidant properties of manganese are vulnerable to iron. Cellular pools of iron can outcompete manganese for binding to manganese superoxide dismutase, and through Fenton chemistry, iron may counteract the benefits of non-proteinaceous manganese antioxidants. In this minireview, we highlight ways in which cells maximize the efficacy of manganese as an antioxidant in the midst of pro-oxidant iron.