In approximately the last 20 years, the self-protection capacity of many American Indian tribes has significantly increased to include the review of research requests by a tribally based IRB. While these tribal IRBs are trained using a curriculum derived from the Belmont Report, there is need to recognize the cultural specificity of the Belmont Report and its potential for conflict or inappropriateness when applied to populations with deep differences in cultural constructs compared to the majority population. However, recognition of the sometimes paradigmatically different culture of American Indian tribes compared to the U.S. culture at large seldom occurs. Moreover, significant and subtle factors of researchers' professional, organizational, and personal cultures that relate to the research enterprise are essentially never addressed by themselves or the tribal IRB. Nonetheless, tribal IRBs continue and serve as a procedural guide for investigators intending to conduct respectful research with American Indian populations.