Over 15 years of research on correlations between superoxide dismutase (SOD) activity and aging or life span have failed to provide a consistent picture of the role of SOD in aging. While genetic manipulations that increase CuZn-SOD activity have only a slight, if any, effect on maximum life span in several species, they do increase resistance to oxidative stress. However, increasing both CuZn-SOD and catalase does significantly increase maximum life span. Decreased SOD expression in a variety of species increases their vulnerability to oxidative stress, and in the case of genetically altered CuZn-SOD, leads to premature death of motor neurons in humans. Little is known about the regulation of expression of SOD and other antioxidant defense enzymes in eukaryotes. The research summarized below collectively suggest that SOD plays an important role in longevity and degenerative disease, but much remains to be learned before manipulation of SOD expression can be considered for effective intervention in either process.