That free radicals and the damage they inflict are related to deteriorative cellular and organismal changes associated with aging and also with the development of a variety of age-related diseases is widely debated. There seems to be little doubt that free radical mutilation of essential molecules contributes to these conditions. Numerous investigators, on the basis of their experimental results, have drawn this conclusion. If the free radical theory of aging and disease development has validity, antioxidants could presumably be successfully used to delay the molecular destruction, cellular loss, and organismal death. In the current review we summarize the experimental data related to the utility of melatonin in protecting against reactive oxygen and reactive nitrogen species-induced cellular damage. While the data supporting a role for melatonin in forestalling aging and prolonging life span per se is not compelling, the findings related to melatonin's ability to reduce the severity of a variety of age-related diseases that have as their basis free radical damage is convincing. To date, the bulk of these investigations have been performed in experimental models of diseases in animals. It is now imperative that similar studies be conducted using humans whose quality of life may benefit from treatment with melatonin.