The granin protein family is composed of two chromogranin and five secretogranin members that are acidic, heat-stable proteins in secretory granules in cells of the nervous and endocrine systems. We report that there is little evidence for evolutionary relationships among the granins except for the chromogranin group. The main granin members, including chromogranin A and B, and secretogranin II are moderately conserved in the vertebrates. Several small bioactive peptides can be generated by proteolysis from those homologous domains existing within the granin precursors, reflecting the conservation of biological activities in different vertebrates. In this context, we focus on reviewing the distribution and function of the major granin-derived peptides, including vasostatin, bovine CgB(1-41) and secretoneurin in vertebrate endocrine systems, especially those associated with growth, glucose metabolism and reproduction.