Here, at the end, it’s appropriate to go back to the beginning—to Dobzhansky’s premise that “nothing in biology makes sense except in the light of evolution”. Is this really true for immunity? We think it is. The value of the light that an evolutionary approach can shed is seen in the regularity with which insights gained from “simpler” systems have led to advances in our understanding of how the mammalian immune system functions. Yet, the light of evolution is not a spotlight, but rather a diffuse source that leaves some aspects of the subject making sense, while others remain under-illuminated. The dark areas are caused in part by the extinctions during phylogeny, which leave the answers to many specific questions, such as the origin of MHC molecules, or the switch from agnathan to gnathostome adaptive immunity, buried in the mists of evolutionary time. In part, they are also due to the fact that invertebrate systems are often felt to be of secondary interest, and hence they remain largely unexplored.