The adaptive immune system has long been considered a key evolutionary innovation of the vertebrates, the product of two rounds of genome duplication that gave rise to the raw material necessary for the evolution of a highly specific immune response and immune memory. While comparative studies of a small number of model organisms have led to the commonly held view that the adaptive immune system has remained relatively static since its origin, recent studies of non-model organisms are challenging this notion, highlighting the fact that we have only begun to scratch the surface in terms of our understanding of immune system diversity. Some of the most exciting recent results have come from the comparative analysis of teleost fishes, a group that includes more than 40% of vertebrates, and shows remarkable diversity in immune system structure and function. Despite the repeated loss of key components of the adaptive immune machinery in this group, affected species are capable of mounting a robust response to immune challenge, suggesting that they have evolved alternative mechanisms of immune protection. Such deviations from the canonical model of vertebrate immunity create opportunities to explore common paradigms of immune function, and may contribute to new experimental approaches and methods of treatment.