Immunological insights from fish. Among vertebrates, teleosts comprise particularly diverse and ancient lineages that can provide alternative immunological solutions to biological and environmental challenges. For example, Atlantic cod is the first species reported that has lost the major histocompatibility complex (MHC) II, one of the antigen presentation systems previously believed to be conserved among all jawed vertebrates, and this loss coincides with a distinct immune gene repertoire. In this issue (pages 648–651), Star and Jentoft propose several scenarios, with different selective assumptions, that may have lead to the emergence of these phenomena. Through comparative studies of immune genes in multiple teleost lineages, we may be able to infer a causal link between the loss of MHC II and the emergence of such distinct immune gene repertoire. Additionally, these studies can identify which biological and environmental factors have promoted their evolution and provide a deeper understanding of the selective processes that have affected the vertebrate immune system.