Neurotrophins are structurally related neurotrophic polypeptide factors that regulate neuronal differentiation and are essential for neuronal survival, neurite growth and plasticity. It has until very recently been thought that the neurotrophin system appeared with the vertebrate species, but identification of a cephalochordate neurotrophin receptor (Trk), and more recently neurotrophin sequences in several genomes of deuterostome invertebrates, show that the system already existed at the stem of the deuterostome group. Comparative genomics supports the hypothesis that two whole genome duplications produced many of the vertebrate gene families, among those the neurotrophin and Trk families. It remains to be proven to what extent the whole genome duplications have driven macroevolutionary change, but it appears certain that the formation of the multi-gene copy neurotrophin and Trk receptor families at the stem of vertebrates has provided a foundation from which the various functions and pleiotropic effects produced by each of the four extant neurotrophins have evolved.