Metalloporphyrins have emerged as a novel class of catalytic antioxidants that scavenge a wide range of reactive oxygen species (ROS) such as superoxide, peroxide, peroxynitrite and lipid peroxyl radicals. Factors such as the type of metal centre, redox potential and electrostatic charge of the compounds are recognized as important determinants of their antioxidant activity and potency. These concepts have guided the development of metalloporphyrins with specific activities greater than those of the native superoxide dismutases. Several compounds in this class have been shown to be efficacious in a variety of in vitro and in vivo oxidative stress models of human diseases.