The problem of pre-nervous neurotransmitter systems arose from studies carried out on different groups of invertebrates and vertebrates in the late 1950s to early 1960s. These investigations were motivated by an hypothesis formulated by K. S. Koshtoyants concerning the similarity between pre-nervous control processes and neuronal functions. Here, we review new data related to the embryogenetic and morphogenetic functions of serotonin (5-HT) and 5-HT-like substances in early embryos of sea urchins, mouse, and other species. Accumulating evidence across animal phyla indicates that 5-HT, together with other classical neurotransmitters, regulates basic developmental processes, including cell proliferation, migration, differentiation, and morphogenesis. Future investigations of cellular and molecular mechanisms underlying phylogenetically old functions of neurotransmitters could provide new insights into the evolutionary emergence of the vertebrate nervous system.