Plague in nature is a flea-transmitted infection of rodents caused by the bacterium Yersinia pestis. Human beings are infected by encountering the complex three-factor natural plague cycle involving the etiologic agent, an arthropod vector, and a vertebrate host. Plague repeatedly had a major impact on human history by altering and upsetting the political structures and population dynamics of communities and countries swept by enigmatic epidemics with high rates of morbidity and mortality. The epidemiology of plague is complex and varies among continents and other major, biologically unique environments. Habitats that support the vertebrate hosts and vector fleas of plague may be considered in three categories, related largely to their importance to humans: commensal, usually urban, domestic rodent habitats; peridomestic, semiurban rodent habitats; and rural or wild rodent habitats. The three basic clinical forms of human plague include bubonic, septicemic, and pneumonic plague.