Acute stroke management practices in rural areas of the United States are suboptimal, which creates an unacceptable health disparity between urban patients with stroke and their rural counterparts. The existing gap between urban and rural stroke care may widen in the future as more urban-tested interventions are incorporated into the treatment of acute stroke. We conducted a PubMed search to identify all the articles published from 1997 to 2007 that addressed acute stroke, paramedics, ambulances, emergency services, and interhospital transportation pertaining to the US rural, urban, or nonurban environment. We review herein the problems and potential solutions that exist in 3 aspects of the current rural stroke care system: prehospital care, rural local hospital emergency department care, and interhospital transfer of patients and subsequent reception at a larger tertiary care institution, which often involve long distances and considerable time. We conclude that the current gap in rural-urban stroke management practices could be overcome with a comprehensive strategy that addresses the existing issues, including further education of rural caregivers, remote support from tertiary care institutions, and implementation of future acute clinical trials that test the rural strategies to stroke care.