Yersinia pestis is the cause of plague, an illness that may manifest in bubonic, pneumonic, or septicemic form. Plague has killed an estimated 200 million humans throughout history, and plague is endemic in many areas of the world. Approximately 2,000 cases of plague are reported each year to the World Health Organization, and concern has been raised about the possible use of Y pestis as an agent of bioterrorism. The genome of Y pestis has been sequenced, including the 3 virulence plasmids, pPst, pLcr, and pFra, and advances have been made in understanding the bacterial pathogenesis of Y pestis infection. Advances also have been made in rapid diagnosis, the understanding of immune responses during plague, and vaccine development.