Given the complex historical context of research with indigenous communities, there is an ethical imperative to ensure cultural sensitivity in research with these populations. Despite this need, there is a lack of practical guidance based on empirical results to conduct culturally sensitive research. The purpose of this qualitative inquiry is twofold. First, Part 1 identifies strategies for culturally sensitive research with indigenous communities in the USA. Second, Part 2 applies culturally sensitive strategies to a specific research setting with an indigenous community. Part 1 uses a qualitative descriptive study with 13 indigenous and non-indigenous researchers to identify strategies for cultural sensitivity in research. Part 2 applies identified strategies to a rigorous critical ethnography with indigenous communities. Emergent themes from Part 1 include the impact of history, relational research, incorporating cultural sensitivity and strengths, demonstrating patience, and negotiating multiple perspectives. These themes inform a researcher’s toolkit for cultural sensitivity, which is applied to a localized setting in Part 2. Cultural sensitivity enhances the quality and usefulness of research, which is better able to address the pressing problems experienced by some indigenous communities.