Cartilaginous fish are the most ancient extant jawed vertebrates possessing bona fide immunoglobulin (Ig) and T-cell receptor molecules. The study of these animals is critical for understanding the origins of the vertebrate immune system. Here, Samuel Schluter, Ralph Bernstein and John Marchalonis review the latest data concerning heavy-chain variable genes and associated isotypes in these animals, and propose a model for the early origins of Igs.