Health service provision has been an aspect of indigenous-United States relationships for over two hundred years, yet America's First Peoples continue to suffer from poor health outcomes when compared with other racial or ethnic groups in the United States. An important change over recent decades is that more and more tribes are managing their own health care services—a realignment of administration and authority that has the potential to substantially improve American Indian and Alaska Native health in years to come. This paper describes the history of health care provision to federally recognized American Indian tribes. It continues by documenting the sparse research literature on tribal management of health care services and identifying information still needed to bring knowledge of this topic up-to-date. Five challenges for tribal management of health-care services that should be considered by tribes and policymakers in their health-care efforts and brought to bear on future research are discussed. By addressing both tribal control of health-care services and the role of tribes in changes to federally provided health care, this paper adds the lens of tribal sovereignty to current discussions of the history and policy context for American Indian and Alaska Native health.