The call for community-based participatory research approaches to address cancer health disparities is increasing as concern grows for the limited effectiveness of existing public health practice and research in communities that experience a disparate burden of disease. A national study of participatory research projects, Research for Improved Health, funded by the National Institutes of Health (2009–2013), identified 64 of 333 projects focused on cancer and demonstrated the potential impact participatory approaches can have in reducing cancer disparities. Several projects highlight the success of participatory approaches to cancer prevention and intervention in addressing many of the challenges of traditional practice and research. Best practices include adapting interventions within local contexts, alleviating mistrust, supporting integration of local cultural knowledge, and training investigators from communities that experience cancer disparities. The national study has implications for expanding our understanding of the impact of participatory approaches on alleviating health disparities and aims to enhance our understanding of the barriers and facilitators to effective community-based participatory research.