Flight activity of insects comprises one of the most intense biochemical processes known in nature, and therefore provides an attractive model system to study the hormonal regulation of metabolism during physical exercise. In long-distance flying insects, such as the migratory locust, both carbohydrate and lipid reserves are utilized as fuels for sustained flight activity. The mobilization of these energy stores in Locusta migratoria is mediated by three structurally related adipokinetic hormones (AKHs), which are all capable of stimulating the release of both carbohydrates and lipids from the fat body. To exert their effects intracellularly, these hormones induce a variety of signal transduction events, involving the activation of AKH receptors, GTP-binding proteins, cyclic AMP, inositol phosphates and Ca2+. In this review, we discuss recent advances in the research into AKH signaling. This not only includes the effects of the three AKHs on each of the signaling molecules, but also crosstalk between signaling cascades and the degradation rates of the hormones in the hemolymph. On the basis of the observed differences between the three AKHs, we have tried to construct a physiological model for their action in locusts, in order to answer a fundamental question in endocrinology: why do several structurally and functionally related peptide hormones co-exist in locusts (and animals in general), when apparently one single hormone would be sufficient to exert the desired effects? We suggest that the success of the migratory locust in performing long-distance flights is in part based on this neuropeptide multiplicity, with AKH-I being the strongest lipid-mobilizing hormone, AKH-II the most powerful carbohydrate mobilizer and AKH-III, a modulatory entity that predominantly serves to provide the animal with energy at rest.