The epidemic of acquired immunodeficiency disease [AIDS] has focused interest on the origins of "new" infectious agents. Great plagues are well known from the distant past, but a number of novel diseases affecting the nervous system infections have emerged in recent years. The causes of such new disorders are diverse: whereas rapid mutations of microbes allow the evolution of truly novel agents, the appearance of new diseases is more often due to changes in human or vector populations or changes in societal mores that result in dissemination of preexistent microbes. Examples of recently emerging infections that involve the nervous system include the enterovirus 70 epidemics with poliomyelitis-like disease, the appearance of California virus encephalitis in the midwestern United States, the rapid spread of Lyme disease with its many neurological complications in the eastern United States, and the outbreak of bovine spongiform encephalopathy in the United Kingdom, in addition to the devastating epidemic of human immunodeficiency virus (HIV), which will cause nervous system disease in over half of those infected. As the world population increases and modern transportation brings us closer into a "global village" more new agents will emerge and more will be sustained. Knowledge of the molecular biology and ecology of the agents and awareness of how our actions can alter their behavior are our best defense.