This article describes the collective experience of a multidisciplinary network of researchers, practitioners, and program evaluators who support appropriate research and evaluation methods in working with Native peoples. Our experience underlines the critical importance of culture in understanding and conducting research with the diverse populations of American Indians and Alaska Natives, and documents the need for community-based, collaborative, participatory action research. We discuss the major findings of the first American Indian Research and Program Evaluation Methodology national symposium, and articulate a set of 20 guiding principles for conducting research and program evaluation.