The proliferation of genomic sequence data in recent years has led to the identification of numerous orthologous and paralogous genes in a variety of divergent taxa. Phylogenetic comparisons of this sequence information have led not only to the construction of improved evolutionary relationships among genes and species, but also led to greater understanding of how genes and their proteins evolve differently throughout the Metazoa. Our recent characterization of a biologically active corticotropin-releasing factor (CRF)-like sequence at the C-terminal region of the teneurin transmembrane proteins has led to a number of questions of how peptide genes evolve and develop new functions in the Metazoa. The teneurin C-terminal associated peptides show structural similarity to the calcitonin family of peptides as well as the CRF family, and like both peptide families, plays a role in the regulation of stress and anxiety.