In 2012, the National Institutes of Health funded the Collaborative Research Center for American Indian Health (CRCAIH) to work toward two broad goals: 1) to build tribal research infrastructure, and 2) to increase research on social determinants of health in American Indian communities. As the introduction to this special issue of American Indian and Alaska Native Mental Health Research, we highlight results from the Partnership River of Life evaluation tool in order to provide broader context for the other manuscripts presented here. Insights were gained during the Partnership River of Life group discussion and evaluation process of combining the groups' rivers to create one representation of the CRCAIH partnership. Detailed results underscore insights for similar transdisciplinary groups.