Novel neuropeptides of G-protein coupled receptor (GPCR) ligands are shown to localize in the brain and perform a range of physiological functions including feeding regulation. Here, we will describe the distribution and localization of these neuropeptides identified very recently and to examine their involvement in neuronal networks, particularly feeding regulation. This review concerns some novel GPCR ligands of feeding-regulation factors such as orexin, ghrelin and galanin-like peptide (GALP), or those described by our research group and others, and neuronal interactions among these neuropeptides in the hypothalamus. Cross-talk among several of these neuropeptide-containing neuron types in the hypothalamus plays a role in determining feeding states. We show structural and functional characteristics of novel neuropeptides and summarize the known interactions between several of these neuron types and leptin-targeting neurons in the hypothalamus. Research in this field will serve an important role in clarifying neurologically-based causes for appetite dysfunctions and help in establishing therapies for people suffering from such conditions.