This chapter describes the unique issues of HIV prevention and treatment in rural areas in the United States. The associated cultural factors can serve as barriers to accessing HIV prevention and treatment services, such as lack of insurance coverage and provider shortages in rural areas. Barriers to receiving health care include provider shortages and inexperience, lack of consistent primary care provider contact despite available Ryan White funds, lack of social support, and stigma. Fear of disclosure, lack of health care and support services, and limited treatment options are barriers to effective prevention and treatment in many rural areas across the country. Rural midwestern communities are characterized by limited access to primary care, self-care education, mental health and family support services, and community educational programs. Online health promotion interventions could be particularly useful for men who have sex with men (MSM) living in rural areas who are at risk for HIV/AIDS.