Research and educational programs have the potential to improve health care. American Indians (AIs) suffer from considerable health disparities as compared with the general U.S. population, including significantly higher incidence and prevalence of preventable diseases like diabetes, alcoholism, and their complications. Underfunding of health programs, including the Indian Health Service, and lower socioeconomic status among AIs contribute to these disparities. Improvements in disease prevention and treatment potentially offered by research and health education programs could help to reduce health disparities. However, a history of nonparticipation in the research process and a history of dishonest research practices have raised barriers to conducting research in AI communities. Additional barriers are generated from a shortage of AI researchers and health care professionals. A research paradigm that includes the community as a full partner is necessary to promote research and education in AI communities and to translate health research into reductions in health disparities.