A historical backdrop of oppression and exploitation has set the stage for distrust in research relationships with many indigenous communities. Although distrust poses a barrier to conducting research with indigenous communities, it also provides a distinct opportunity to examine factors related to trust development. Therefore, the purpose of this article is to understand the factors that relate to trust development in research relationships with indigenous communities in the United States. This qualitative descriptive study explored the experiences of 13 indigenous and non-indigenous researchers working with indigenous communities. Historical oppression, risk and reputation, power balancing across multiple levels, reciprocity and benevolence, and cross-cultural collaboration were emergent themes related to trust development with indigenous communities. Activities between researchers and indigenous communities occurred within a broader context of historical oppression and were on a continuum between trust-building and trust-breaking.