Peptides are ancient signaling systems that are found in almost all animals on Earth. Genome sequencing reveals evidence of neuropeptide genes in Cnidaria, Ctenophora, and Placozoa, some of oldest living animals with nervous systems or neural-like tissues. Recent studies also show genomic evidence of neuropeptide processing machinery in metazoans and choanoflagellates, suggesting that neuropeptide signaling may predate the development of nervous tissues. Additionally, Ctenophore and Placozoa neural signaling is entirely peptidergic and lacks the major amine neurotransmitters such as acetylcholine, dopamine, and serotonin. This also suggests that neuropeptide signaling developed before amine neurotransmitters.