In fish, the structural and functional characteristics of insulin and IGF-I receptors have been well studied. Current evidence indicates that all gnatostome animals, from fish to mammals, contain separate insulin and IGF-I molecules and specific receptors for insulin and IGF-I. However, qualitative differences in the functional aspects of insulin and IGF-I receptors among vertebrate species can account for variations in the biological activity of insulin and IGF-I. In this paper we will focus on the functional evolution of the insulin and IGF-I receptors in vertebrates and on the appearance of the unrelated IGF-II receptors.