Collaborative and participatory research approaches have received considerable attention as means to understanding and addressing disparities in health and health care. In this article, the authors describe the process of building a three-way partnership among two academic health centers-Duke University and the University of North Carolina-and members of the Latino community in North Carolina to develop and pilot test a lay health advisor program to improve Latina immigrants' mental health and coping skills. The authors applied the principles of participatory research to engage community and academic partners, to select the health topic and population, and to develop program goals and objectives. Key challenges were negotiating administrative structures and learning institutional cultures, as well as dealing with contextual issues such as mental health reform and antiimmigrant sentiment in the state.Some important lessons learned are to seek opportunities for taking advantage of existing relationships and expertise at each academic institution, to be respectful of the burden of research on vulnerable communities, and to involve community partners at all stages of the process.