In humans, several pathologies involve the overproduction of reactive oxygen species. Metal-containing catalytic antioxidants have emerged as a novel class of potential therapeutic agents that scavenge a wide range of reactive oxygen species. There are three structural classes of manganese-containing catalytic antioxidants that have efficacy in several oxidative stress models of human disease. The classes are divided based on their in vitro selectivity towards the scavenging of superoxide. The selective catalytic antioxidants include the macrocyclics, whereas the non-selective catalytic antioxidants include the salens and porphyrins. Cardiovascular, neurodegenerative and inflammatory lung disorders are all potentially important targets for catalytic antioxidant therapy.