This article describes the activities of the Indigenous Wellness Research Institute (IWRI) at the University of Washington, Washington State, in collaborating with tribal colleges and universities (TCUs) to examine alcohol, drug, and mental health issues among Native students. The authors provide first steps for the development of culturally appropriate and sustainable alcohol and drug abuse treatment and prevention strategies that have enhanced postsecondary academic success among Native students. Community-based participatory research approaches that engage tribal communities in decision-making and power-sharing are the continued goals of the TCU-IWRI.