RFamide peptides that possess the Arg-Phe-NH2 motif at their C-termini have been characterized in invertebrates and vertebrates. The first RFamide peptide was the cardioexcitatory peptide Phe-Met-Arg-Phe-NH2 (FMRFamide), which was isolated from the ganglia of the Venus clam Macrocallista nimbosa. In the past, the existence of five groups within the RFamide peptide family has been recognized in vertebrates: the gonadotropin-inhibitory hormone (GnIH) group, the kisspeptin group, the PQRFamide peptide (NPFF) group, the pyroglutamylated RFamide peptide (QRFP)/26RFamide group, and the prolactin-releasing peptide (PrRP) group. These RFamide peptides have been shown to exert important neuroendocrine, behavioral, sensory, and autonomic functions. This chapter summarizes the structural features and functions of RFamide peptides and their cognate receptors.