Community-based participatory research (CBPR), with its emphasis on joining with the community as full and equal partners in all phases of the research process, makes it an appealing model for research with vulnerable populations. However, the CBPR approach is not without special challenges relating to ethical, cultural, and scientific issues. In this article, we describe how we managed the challenges we encountered while conducting a CBPR project with a Native American community. We also suggest criteria that will enable evaluation of the project.