Pulses of the steroid hormone 20-hydroxyecdysone (ecdysone) regulate diverse biological responses during the life history of insects. Studies of the fruit fly, Drosophila melanogaster, have provided significant insights into the mechanisms underlying ecdysone mediated regulation of development. During the dramatic metamorphosis of Drosophila, ecdysone induces the histolysis of nearly all of the larval tissues and differentiation and morphogenesis of the structures composing the adult fly. These changes are mediated by a genetic signaling cascade that was first recognized as puffs in the giant polytene chromosomes of the salivary gland. This genetic regulatory cascade is composed of early and late genes that are intricately coordinated by changes in hormone titer. Early genes encode regulatory proteins that are involved in the proper regulation of late genes, which are thought to play a more direct role in development. The regulation and function of these genes is discussed in the context of the cell- and tissue-specific changes required for the reorganization of a larva to form an adult fly.