Yersinia pestis, the etiologic agent of bubonic plague is the most virulent bacterial human pathogen. This presentation discusses the history of plague and how recent genomic analyses of Neolithic and Bronze Age human skeletal remains trace the evolution of a ‘mild’ pathogen to one that can cause devastating pandemics. Scott A. Minnich is a professor in the Department of Animal, Veterinary and Food Sciences and the IDeA Network of Biomedical Research Excellence.