The nature of the HIV epidemic in the United States and Canada has changed with a shift toward rural areas. Socioeconomic factors, geography, cultural context, and evolving epidemics of injection drug use are coalescing to move the epidemic into locations where populations are dispersed and health care resources are limited. Rural-urban differences along the care continuum demonstrate the implications of this sociogeographic shift. Greater attention is needed to build a more comprehensive understanding of the rural HIV epidemic in the United States and Canada, including research efforts, innovative approaches to care delivery, and greater community engagement in prevention and care.