Neuropilin-1 (NRP1) and neuropilin-2 (NRP2) are transmembrane glycoproteins that have been characterized as receptors for both semaphorins for neuronal guidance and vascular endothelial growth factor (VEGF) for angiogenesis. Biologic properties of NRPs have been linked to their unique domain structures. However, molecular interaction among NRPs, VEGF, and VEGF receptors is still not clear. Although several types of cancer cells can express NRPs, the role of NRPs in tumor pathogenesis is largely unknown. Thus, future investigations should include determining the effects and mechanisms of NRPs on proliferation, apoptosis, and migration of neuronal , endothelial, and cancer cells. Study of protein-protein interaction, signal transduction pathways, and NRP-mediated gene expression is particularly important to understand NRPs functions, which may have significant clinical applications in the treatment of neurological disorders, cardiovascular diseases, and certain cancers.