The paper focuses on the challenges in conducting research in Native American communities and provides a multi-step model for developing, implementing and evaluating drug abuse prevention programs in partnership with Native American communities. Key steps in the model include building collaborative relationships with community members, developing interventions to fit local culture and norms, training indigenous staff to implement the program(s) and obtaining ongoing feedback from participants, using both qualitative and quantitative methods. A case study, the Native American Prevention Project Against AIDS and Substance Abuse, serves to illustrate how integrating cultural and community input into a project can lead to empowerment of community members and successful program outcomes. Note, figure, references