Dietary caloric restriction is the most reproducible means of extending longevity and maintaining health and vitality. It has been shown to be relevant to a wide rage of species, including primates. Examination of key markers of the calorically restricted phenotype, such as plasma insulin, dehydroepiandrosterone sulfate, and body temperature, suggest that they may predict longevity in humans as well. However, most people would be unwilling or unable to adopt the 30% to 40% reduction in food intake necessary to achieve optimal health and longevity benefits. For this reason, a number of laboratories are pursuing caloric restriction mimetics: ways to achieve the benefits of restriction without eating less. This approach will undoubtedly remain a major focus of biogerontology for the foreseeable future.