The neuropilin receptors were first discovered as regulators of nervous system development, acting as semaphorin coreceptors with plexins. Subsequently, the neuropilins were identified as receptors for vascular endothelial growth factor. Since those seminal discoveries, additional ligands that bind neuropilins have been described, and many studies have implicated neuropilins in playing key roles in tumor biology. Recent evidence has shown that manipulating neuropilin function can regulate tumor growth and metastasis through effects on vascular biology in the case of neuropilin-1 and lymphatic biology in the case of neuropilin-2. A direct role for neuropilins within in tumor cells has also been postulated. As data continue to accumulate pointing to a role for neuropilins in cancer, the promise for targeting this pathway is beginning to unfold.