Since 1993, 14 American Indian and Alaska Native (AIAN) communities have worked diligently to reduce the harm due to substance abuse in their communities. Funded by the Robert Wood Johnson Foundation's Healthy Nations Initiative I, these communities implemented creative strategies that span the continuum from community-wide prevention, early identification and treatment to aftercare. Drawing upon the unique strengths of their own cultural traditions to find solutions to local substance abuse problems, these efforts have identified important and useful lessons for not only other AIAN communities, but also for sponsors of substance abuse programming in Indian country and elsewhere. Described here are successful strategies for developing and sustaining substance abuse programs in AIAN communities and an assessment of their impacts and accomplishments.