Neuropeptides are ubiquitous signaling molecules that underpin almost all brain functions. They mediate extrasynaptic communication in nervous systems predominantly by binding to cell surface G protein-coupled receptors (GPCRs). The number of neuropeptide pathways is diverse and peptide-activated GPCRs are widely expressed throughout the brain, forming an extensive signaling network. To understand the structure and organization of this network, we have mapped the neuropeptide-receptor signaling network in the nervous system of C. elegans. Systematic mapping of peptide-GPCR pairs, using reverse pharmacology, reveals different types of ligand-receptor interactions, allowing binary and combinatorial signaling, and shows broad evolutionary conservation of neuropeptide pathways in C. elegans. By integrating this interaction network with gene expression datasets, we have constructed a brain-wide map of neuropeptide signaling in C. elegans. The topology of the neuropeptide network differs from that of other communication networks, such as synaptic connectomes, and displays typical features including extended signaling cascades, feedback loops, and combinatorial neuropeptide modulation. The structure of neuropeptide signaling networks is also sculpted by experience during learning and adaptation to environmental changes. Building on this network map, we are investigating how neuropeptide networks are functionally organized and developing in vivo neuropeptide sensors to better understand network plasticity.