This perspective draws on the record of ancient pathogengenomes and microbiomes illuminating patterns of infectious disease over the course of the Holocene in order toaddress the following question. How did major changes inliving circumstances involving the transition to and intensification of farming alter pathogens and their distributions? Answers to this question via ancient DNA researchprovide a rapidly expanding picture of pathogen evolution and in concert with archaeological and historical data, give a temporal and behavioral context for heath in the past that is relevant for challenges facing the world today, including the rise of novel pathogens.