Our views of both innate and adaptive immunity have been significantly modified by recent studies of immune receptors and immunity in protostomes, invertebrate deuterostomes, and jawless vertebrates. Extraordinary variation in the means whereby organisms recognize pathogens has been revealed by a series of recent findings, including: novel forms of familiar immune receptors, high genetic polymorphism for new receptor types, germline rearrangement for non-Ig domain receptors, somatic variation of germline-encoded receptors, and unusually complex alternative splicing of genes with both immune and non-immune roles. Collectively, these observations underscore heretofore unrecognized pathways in the evolution of immune recognition and suggest universal processes by which immune systems co-opt and integrate existing cellular mechanisms to effect diverse recognition functions.