VIP and PACAP are two prominent neuropeptides that share two common G protein-coupled receptors, VPAC1 and VPAC2, while PACAP has an additional specific receptor, PAC1. This article reviews the present knowledge regarding various aspects of VPAC receptors including: 1) receptor specificity toward natural VIP-related peptides and pharmacology of synthetic agonists or antagonists; 2) genomic organization and chromosomal localization; 3) signaling and established or putative interactions with G proteins or accessory proteins such as RAMPs or PDZ-containing proteins; 4) molecular basis of ligand-receptor interaction as determined by site-directed mutagenesis, construction of receptor chimeras, and structural modeling; 5) constitutively active receptor mutants; 6) short-term (desensitization, internalization, phosphorylation) and long-term (transcription) regulations and transgenic models; 7) receptor polymorphisms.