The worldwide prolongation of mean life expectancy has resulted in a rapid increase of the size of the elderly population, both in numbers and as a proportion of the whole. In addition, the incidence of age-related diseases is obviously increasing as the population ages. Finding means to preserve optimal health in old age has become a primary goal of biomedical research. Aging is a multifactorial process that includes progressive cellular loss, endocrine and metabolic deficits, reduced defense mechanisms and functional losses that increase the risk of death. Mitochondria fulfill a number of essential cellular functions and play a key role in the aging process. Melatonin, which is synthesized in the pineal gland and other organs, plays a role in the biologic regulation of aging. Noctural melatonin serum levels are high during childhood and diminish substantially as people age. Melatonin preserves mitochondrial homeostasis, reduces free radical generation, e.g., by enhancing mitochondrial glutathione levels; it also safeguards proton potential and ATP synthesis by stimulating complex I and IV activities. In this article, we review the role of melatonin and mitochondria in aging.