The mechanisms of aging are still largely a mystery. However, recent studies using yeast, C. elegans, and Drosophila show that longevity can be altered by genetic manipulations. Moreover, drugs increase lifespan of these organisms have been identified. An anticonvulsant ethosuximide, antidepressants such as mianserin, antioxidants, an inhibitor of histone deacetylase, and resveratrol, a Sir2 activator, significantly extend lifespan of some organisms. Although these drugs have not been reported to extend lifespan of mammals, they provide molecular cues to elucidate aging mechanisms.