Increasingly, Tribal Nations are forming ethics review panels, which function separately from institutional review boards (IRBs). The emergence of strong community representation coincides with a widespread effort supported by the U.S. Department of Health & Human Services and other federal agencies to establish a single IRB for all multi-site research. This article underscores the value of a tribal ethics review board and describes the tribal oversight for the Safe Passage Study-a multi-site, community-based project in the Northern Plains. Our experience demonstrates the benefits of tribal ethics review and makes a strong argument for including tribal oversight in future regulatory guidance for multi-site, community-based research.