Transitions between different states of development, physiology, and life history are typically mediated by hormones. In insects, metamorphosis and reproductive maturation are regulated by an interaction between the sesquiterpenoid juvenile hormone (JH) and the steroid 20-hydroxy-ecdysone (20E). In vertebrates and some marine invertebrates, the lipophilic thyroid hormones (THs) affect metamorphosis and other life history transitions. Interestingly, when applied to insects, THs can physiologically mimic many facets of JH action, suggesting that the molecular actions of THs and JH/20E might be similar. Here we discuss functional parallels between TH and JH/20E signaling in insects, with a particular focus on the fruit fly, Drosophila melanogaster, a genetically and physiologically tractable model system. Comparing the effects of THs with the well defined physiological roles of insect hormones such as JH and 20E in Drosophila might provide important insights into hormone function and the evolution of endocrine signaling.