Since Harman in 1972 first proposed a role in the process of aging for the mitochondrial genome, a wealth of evidence has been accumulated to support this theory. We discuss the hereditary mitochondrial DNA disorders, which we believe may give insight into both normal aging and neurodegenerative conditions. We then review the evidence for the role of mitochondrial DNA mutations in both aging and age-related disorders and also discuss new approaches for investigating the mitochondrial genome at a single cell level, by observing the activity of the mitochondrial enzyme cytochrome c oxidase.