The high incidence of age-related diseases in the increasing population of elderly people has stimulated interest in the search for protective agents that have the capability of preventing premature aging and delaying the onset of degenerative disorders. To preserve health in old age becomes a primary goal for biomedicine, because the increasing longevity in our societies is associated with a rise in morbidity. The difficulties in finding new approaches and safe strategies for prevention, intervention, and treatment are related to the lack of theoretical background as well as to insufficient models to test the efficacy of anti-aging agents. Melatonin is a prime candidate for slowing the aging process and targeting its underlying pathology. Melatonin has profound gerontoprotective and antioxidant activities. Because enhanced oxidative stress plays a crucial role in the aging process and chronic diseases associated with senescence, the adminstration of a potent amphiphilic antioxidant agent with high bioavailability such as melatonin may become a promising, safe, and effective intervention strategy to slow aging and the initiation and progression of age-related disorders. Investigations on melatonin and its anti-aging activity may be of great benefit in increasing life quality of the elderly.