Neuropeptides are molecular messengers that regulate multiple functions in the central nervous system and in the periphery via G-protein-coupled receptors. These signaling peptides have also been identified as potent cellular growth factors for normal cells and they participate in autocrine/paracrine stimulation of tumor cell proliferation and migration. Recent studies on the signaling pathways activated by mitogenic neuropeptides revealed previously unsuspected connections and complexities, including the realization that these receptors not only stimulate the synthesis of conventional second messengers but also induce tyrosine phosphorylation cascades. A major task for the future will be to identify all the contributing molecules, define their functional importance and elucidate the spatiotemporal relationships of this complicated signaling network. As our understanding of the role of neuropeptides in cancer increases, novel possibilities for translational research are emerging for improving the diagnosis and treatment of the disease.