The face of America is changing. In efforts to provide services to and meet the needs of consumers of different ethnicities and cultures, cultural competence has become a driving force not only in health care but also in business, education, and research. Lack of cultural competence among caregivers has been linked to health disparities, decreased client satisfaction, and decreased client adherence to recommended medical regimens. The depth of rural research in general, and by nurse researchers focusing on rural cultural groups in particular, is limited. This chapter focuses on conducting rural nursing research with rural cultural groups, highlights methodological issues that are commonly encountered with rural populations, and proposes strategies to address them. Addressing methodological challenges will contribute to the limited knowledge base related to culture and ethnicity in rural nursing research.