Understanding of peptide hormone evolution rests primarily on structural information, either direct or inferred. We summarize studies of fishes and amphibians to provide initial information within the vertebrate lineage for selected peptides which exhibit varying structural heterogeneity. For these peptides, thyrotropin-releasing hormone, somatostatin, luteinizing hormone-releasing hormone and cholecystokinin related peptides manifest increasing diversification. Members of these peptide families are found distributed among a variety of tissues (e.g., brain, gut, skin, retina, sympathetic nervous system), yet the number of genes encoding for individual types of peptides is presently uncertain. We emphasize the need for additional structural information, for a more thorough and diverse taxonomic investigation within the vertebrate lineage, and for specification of those genetic elements which ultimately determine evolutionary opportunities for peptide evolution.