Study of model parasite-host systems shows that the strength of selection imposed on particular immune genes is strong, and can result in some of the fastest evolutionary rates known for metazoans. In other words, parasite-host immune interactions strongly influence anagenesis, the evolutionary changes occurring within parasite or host lineages. If we adopt a broader perspective with a longer time frame, it seems likely such intense interactions will be seen to have an impact on cladogenesis, the origin of lineages, as well. It seems the overall impact of infection and immunity should attract as much attention as predation, competition, or other biotic interactions in shaping the overall diversity of animal life. Needed are more empirical studies over longer time www.frontiersin.org frames to provide more specific mechanistic insights as to how host immune responses drive diversification of parasites and how this can lead to speciation events, potentially in both parasite and host lineages. Further revelation of specific genes, often not considered part of the immune system per se, and how they facilitate defense against particular parasites and might favor evolutionary divergence among parasites are needed. Finally, placing immunology in a macroevolutionary perspective can hopefully provide insights for understanding today's world in which a host of rapid changes greatly increase the odds for extinction of many animals.