Backgraound. We have been repeatedly asked to clarify genetic issues that have cultural ramifications for Native communities. Method. In the following commentary, we explain selected genetic issues that may vary among tribal nations; nonetheless, scientists should allocate sufficient time to meet with the tribal leaders and/or members of the tribal institutional review board prior to designing a genetic study to learn how selected issues are perceived by that specific tribal nation. Results. Tribal nations generally encourage and mandate community-based participatory research methodology. Conclusions. We have included in this commentary draft language for study protocols to support researchers and tribal nations when developing studies pertaining to genetic issues.