Investigations of American Indian and Alaska Native (AI/AN) populations suggest patterns of mortality that differ from the general population. Mortality data reveal excess overall mortality among AI/ANs, as well as excesses for specific causes of death, including accidents, diabetes, liver disease, pneumonia/influenza, suicide, homicide, and tuberculosis. A relative deficit of deaths has been noted for heart disease, cancer, and HIV infections. It is important that physicians demonstrate cultural competence so they may provide quality medical care for the populations they serve. Activities such as provider education, risk assessment, and emphasis on preventive services are offered to facilitate integration into teaching curricula. Knowledge of distinctive mortality patterns among AI/ANs will help clinicians recognize the unique needs of these patients.