This PRISMA style literature review was used to explore substance abuse studies focused on Native American populations in the context of historical trauma (from experiences at Indian boarding schools) and the critical loss of family relationships from colonization. It was found that while Indian boarding schools are recognized as being important research topics related to substance use, they are usually mentioned as a part of the colonization process rather than examined for their specific historical/personal impacts. Furthermore, social science may fail to recognize how detrimental the loss of family relationships was to the traditional bond of a Native American family. Beginning with an extensive list of 402 articles, two criteria were used to arrive at a systematic list of research in the topic areas: the acknowledgment of Indian boarding school attendance and the impact on family relationships. The final list included 27 studies which looked at Indian boarding schools and family relationship's relation to substance use among Native Americans. Overall, this review revealed that family discord should not be singled out as a causal link for Native American families; rather, it should be included in the argument to explain the relationship between Indian boarding school attendance and substance use.