Trophic interactions in the vertebrate nervous system enable the adjustment of cell number and axon guidance, targeting and connectivity. Computational analysis of the sequenced Drosophila genome failed to identify some of the main trophic factors, the neuregulins and neurotrophins, as well as many other genes. This provoked speculations that the Drosophila nervous system might not require such regulative interactions. Here we review abundant cellular, genetic and functional data that demonstrate the existence of both neurotrophic and gliatrophic interactions in the Drosophila nervous system. Glial survival is maintained by the epidermal growth factor receptor (EGFR) signaling pathway in response to the ligands Spitz, a transforming growth factor-alpha (TGF-alpha) signaling molecule, and Vein, a neuregulin homologue. Cellular and genetic evidence predicts the existence of neuronal trophic factors operating at least in the Drosophila embryo during axon guidance and, in the visual system, during the targeting of retinal axons in the brain.