Population genetics and comparative genomics analyses of the pathogenic Yersinia species have indicated that arthropodborne transmission is an evolutionarily recent adaptation in Yersinia pestis, the agent of plague. We show that the infectivity of Y. pestis to its most proficient vector, the rat flea Xenopsylla cheopis, and subsequent transmission efficiency are both low. The poor vector competence of fleas likely imposed selective pressure that favored the emergence and continued maintenance of a hypervirulent Y. pestis clone. In particular, the rapidly fatal gram-negative sepsis that typifies plague is a consequence of the high threshold bacteremia level that must be attained to complete the transmission cycle. Epidemiological modeling predicts that, to compensate for a relatively short period of infectivity of the mammalian host for the arthropod vector, plague epizootics require a high flea burden per host, even when the susceptible host population density is high.