Approximately three-quarters of human disease loci have counterparts in the fruit fly Drosophila melanogaster. This model organism is therefore extremely valuable for using to understand the role of these loci in normal development, and for unravelling genetic pathways in which these loci take part. Important advantages for Drosophila in such studies are its completed genome, the unparalleled collection of mutations already in existence, the relative ease in which new mutations can be generated, the existence of convenient techniques for inactivating or overexpressing genes in dispensable tissues that are easily observed and measured, and the ability to readily carry out second-site modifier genetics. Recent work in Drosophila on the insulin-signaling pathway, a pathway of profound clinical importance, is reviewed as an illustration of how such research can provide fundamental insights into the functions of this pathway in regulating growth and development. Moreover, Drosophila research is now identifying heretofore unknown regulators of insulin signaling, as well as indicating novel functions for this pathway in suppressing benign tumor formation and regulating life span.