Aging was thought to be a haphazard process, which was not driven by any defined mechanisms. Recently, it has been reported that changing in single gene expression can extend lifespan. Many mutations that extend lifespan are involved in endocrine signaling. The mechanisms of longevity by such mutations are conserved among various species ranging from yeast to mice. One of the most important pathways underlying the regulation of longevity is the insulin signal pathway. In this review, we will describe long-lived animals that have mutations in this pathway and discuss the relationship between insulin signaling, diabetes, and longevity.