On October 20, 2007, a Minnesota resident died from rabies, approximately 1 month after initial symptoms of limb paresthesia, which progressed to flaccid weakness and ataxia. This was the only human rabies case reported in the United States in 2007. A presumptive diagnosis of idiopathic transverse myelitis was considered initially, because of abnormalities detected via spinal cord imaging studies and a lack of laboratory confirmation of a specific infectious etiology. The presumptive diagnosis subsequently was changed to include rabies, based on the patient's rapidly deteriorating neurologic status and elicitation of a history involving bat exposure during the month before illness onset. This report summarizes the medical and epidemiologic investigation by the Minnesota Department of Public Health and CDC and the ensuing public health response. The findings underscore the need for early inclusion of rabies in the differential diagnosis of rapidly progressive encephalitis, improved public awareness of the risks associated with animal bites, and appropriate rabies prophylaxis after exposure.