BACKGROUND: Tribal communities in the United States (U.S.) have a long history of subjection to unethical and exploitive medical and research practices. Today, many Tribal nations are establishing procedures in order to protect themselves from further harm and to advance culturally informed research practices. These procedures are also meant to ensure that their communities benefit from research conducted within their communities. Informed consent is a key element in protecting human subjects, but it may not be sufficient in the tribal context, as its conception is rooted in Western understandings of protection. Specifically, the informed consent emphasizes the individual, rather than the community as a whole, which is just as important in the context of conducting research with Native communities.METHODS: We conduct a systematic literature review to answer two related questions: How is informed consent being conceived of by U.S. tribes? And how is informed consent being required by U.S. tribes? Our inclusion criteria include articles focusing on informed consent within the U.S. tribal context, written in English in 2010-2020. Articles that did not fit our inclusion criteria were excluded. Two reviewers independently reviewed and coded 30 peer-reviewed articles by using content analysis and, in an iterative process, agreed on emerging codes and themes. RESULTS: A number of themes arise in the selected literature, including the conception of informed consent as a process, its operation at various levels (individual, collective, and government-to-government), possible alternatives to informed consent, and the need for specificity about ownership of samples and data, benefits and/or risks, and the methods and procedures that researchers use in the course of study.CONCLUSIONS: Our key results point to a need for clear and transparent information for prospective research participants and for consent forms and processes to include the collective, as well as the individual. This will better align with the cultural values and political standing of sovereign tribes in the U.S.