Monkeypox, a viral disease related to smallpox, has appeared in humans in the Midwest. Though monkeypox usually has a fatality rate of 1 to 10%, no fatalities have occurred in the outbreak, which has been linked to pet rodents. Although officials do not believe that this outbreak is bioterrorism, the delay between the initial presentation of an unusual disease and the notification to the federal government has raised concerns regarding the state of bioterrorism preparedness. The Centers for Disease Control and Prevention (CDC) have provided guidance to local communities regarding handling of ill patients and animals, treatment regimens, and sample protocols. The CDC have recommended and released smallpox vaccine as prophylaxis against monkeypox infection. The CDC and the Food and Drug Administration banned interstate commerce in prairie dogs and certain other rodents and the CDC suspended import of all rodents from Africa. Possible issues related to this outbreak include the regulatory process that allowed import of diseased animals; how efficient the public health system response has been in alerting the government to potential health emergencies; and whether the monkeypox outbreak provides an opportunity to evaluate recent efforts to increase public health preparedness and the state of bioterrorism preparedness. This report will be updated as events warrant.