Neuropeptides are a diverse class of signalling molecules that are widely employed as neurotransmitters and neuromodulators in animals, both invertebrate and vertebrate. However, despite their fundamental importance to animal physiology and behaviour, they are much less well understood than the small molecule neurotransmitters. The neuropeptides are classified into families according to similarities in their peptide sequence; and on this basis, the FMRFamide and RFamide-like peptides, first discovered in molluscs, are an example of a family that is conserved throughout the animal phyla. In this review, the literature on these neuropeptides has been consolidated with a particular emphasis on allowing a comparison between data sets in phyla as diverse as coelenterates and mammals. The intention is that this focus on the structure and functional aspects of FMRFamide and RFamide-like neuropeptides will inform understanding of conserved principles and distinct properties of signalling across the animal phyla.