The last 5 years has seen an explosion of evidence linking RPTPs to the regulation of axon growth and guidance. Important questions to be addressed include the ligand-receptor interactions involved in axon growth regulation, the signaling pathways controlled by RPTPs in neurons, and the manner in which different RPTPs within a class, and different classes of RPTPs, coordinate their functions to ensure appropriate axon growth. Are RPTPs signaling ligands, signaling receptors, or both? Do RPTPs function mainly by modifying adhesive preferences, or are they instructive in guidance decisions? Do specific types of RPTPs send specific signals to neurons, or do they work together to fine-tune levels of tyrosine phosphorylation? Whatever the outcome, it seems certain that the answers to these questions will come only from a combination of the powerful genetic approaches possible in Drosophila (and in mice) with the biochemical and cell biological approaches possible in the vertebrate systems.