Community-based participatory research (CBPR) has emerged in the past decades as an alternative research paradigm, which integrates education and social action to improve health and reduce health disparities. More than a set of research methods, CBPR is an orientation to research that focuses on relationships between academic and community partners, with principles of colearning, mutual benefit, and long-term commitment and incorporates community theories, participation, and practices into the research efforts. As CBPR matures, tensions have become recognized that challenge the mutuality of the research relationship, including issues of power, privilege, participation, community consent, racial and/or ethnic discrimination, and the role of research in social change. This article focuses on these challenges as a dynamic and ever-changing context of the researcher-community relationship, provides examples of these paradoxes from work in tribal communities, discusses the evidence that CBPR reduces disparities, and recommends transforming the culture of academia to strengthen collaborative research relationships.