In May of this year, an outbreak of sudden, unexplained, and highly fatal respiratory illness of unknown etiology was identified in the four-corners region of the southwestern United States. Within 3 weeks after the collaborative response launched by the state and local health agencies in the affected area, laboratory studies from the federal Centers for Disease Control and Prevention suggested that an acute infection with a previously unrecognized Hantavirus species was responsible for the reported cluster of cases. The hantavirus associated with this outbreak has since been isolated in tissue culture, and diagnostic test systems specific for the newly identified hantavirus have been developed. This article summarizes the history of the outbreak as experienced by investigators from the Arizona Department of Health Services and reviews the epidemiologic and clinical aspects of both the current epidemic and hantaviruses in general. The sudden occurrence of acute illnesses in the Southwest due to a previously unrecognized hantavirus reaffirms that the potential for the emergence of new infectious diseases exists at any place or time in the United States. The response to the outbreak also illustrates how community clinicians and federal, state, and local health agencies work together to promptly identify the emergence of new disease threats, rapidly determine new etiologic agents, and develop and swiftly implement appropriate disease prevention and control strategies.