Prevention research aims to address health and social problems through the use of systematic strategies for affecting change and documenting such change. To produce meaningful and lasting results at the level of the community, prevention research frequently requires reevaluating the boundaries that have traditionally separated investigators from the subjects of their investigations. New tools and techniques are required to facilitate such collaborations between researchers and communities while still maintaining scientific rigor. In this paper, we describe the Tribal Participatory Research (TPR) approach, which was developed to facilitate culturally centered prevention research in American Indian and Alaska Native communities. We discuss this approach within the broader context of community-based participatory research, an increasingly prevalent paradigm in the prevention field. We also reflect upon the strengths and limitations of TPR that we have experienced over the past decade.