Insect neurohormones (biogenic amines, neuropeptides, and protein hormones) and their G protein-coupled receptors (GPCRs) play a central role in the control of behavior, reproduction, development, feeding and many other physiological processes. The recent completion of several insect genome projects has enabled us to obtain a complete inventory of neurohormone GPCRs in these insects and, by a comparative genomics approach, to analyze the evolution of these proteins. The red flour beetle Tribolium castaneum is the latest addition to the list of insects with a sequenced genome and the first coleopteran (beetle) to be sequenced. Coleoptera is the largest insect order and about 30% of all animal species living on earth are coleopterans. Some coleopterans are severe agricultural pests, which is also true for T. castaneum, a global pest for stored grain and other dried commodities for human consumption. In addition, T. castaneum is a model for insect development. Here, we have investigated the presence of neurohormone GPCRs in Tribolium and compared them with those from the fruit fly Drosophila melanogaster (Diptera) and the honey bee Apis mellifera (Hymenoptera). We found 20 biogenic amine GPCRs in Tribolium (21 in Drosophila; 19 in the honey bee), 48 neuropeptide GPCRs (45 in Drosophila; 35 in the honey bee), and 4 protein hormone GPCRs (4 in Drosophila; 2 in the honey bee). Furthermore, we identified the likely ligands for 45 of these 72 Tribolium GPCRs. A highly interesting finding in Tribolium was the occurrence of a vasopressin GPCR and a vasopressin peptide. So far, the vasopressin/GPCR couple has not been detected in any other insect with a sequenced genome (D. melanogaster and six other Drosophila species, Anopheles gambiae, Aedes aegypti, Bombyx mori, and A. mellifera). Tribolium lives in very dry environments. Vasopressin in mammals is the major neurohormone steering water reabsorption in the kidneys. Its presence in Tribolium, therefore, might be related to the animal's need to effectively control water reabsorption. Other striking differences between Tribolium and the other two insects are the absence of the allatostatin-A, kinin, and corazonin neuropeptide/receptor couples and the duplications of other hormonal systems. Our survey of 340 million years of insect neurohormone GPCR evolution shows that neuropeptide/receptor couples can easily duplicate or disappear during insect evolution. It also shows that Drosophila is not a good representative of all insects, because several of the hormonal systems that we now find in Tribolium do not exist in Drosophila.