The oxidizing nature of the extracellular environment is vastly different from the highly reducing nature of the intracellular compartment. The redox potential of the cytosolic compartment of the intracellular environment limits disulfide bond formation, whereas the oxidizing extracellular environment contains proteins rich in disulfide bonds. If not for an extracellular antioxidant system to eliminate reactive oxygen and nitrogen species, lipid peroxidation and protein oxidation would become excessive, resulting in cellular damage. Many reviews have focused on the role of intracellular antioxidants in the elimination of oxidative stress, but this one will focus on the coordinated action of both intracellular and extracellular antioxidants in limiting cellular oxidant stress. (Circ J 2008; 72: 1 - 16)