The insulin/IGF-1 pathway has been shown to affect lifespan and rate of aging in a variety of animals including worms, flies and mice. Genetic variation in this pathway may also affect human longevity. We review the evidence for the effect of this pathway on longevity with a focus on the genetic studies in humans to date. One gene, FOXO3A, a transcriptional factor homologous to daf-16, has been repeatedly associated with increased lifespan in several studies in different ethnic populations.