Drosophila melanogaster is since decades the most important invertebrate model. With the publishing of the genome sequence, Drosophila also became a pioneer in (neuro)peptide research. Neuropeptides represent a major group of signaling molecules that outnumber all other types of neurotransmitters/modulators and hormones. By means of bioinformatics 119 (neuro)peptide precursor genes have been predicted from the Drosophila genome. Using the neuropeptidomics technology 46 neuropeptides derived from 19 of these precursors could be biochemically characterized. At the cellular level, neuropeptides usually exert their action by binding to membrane receptors, many of which belong to the family of G-protein coupled receptors or GPCRs. Such receptors are the major target for many contemporary drugs. In this chapter, we will describe the identification, localization and functional characterization of neuropeptide-receptor pairs in Drosophila melanogaster.