In 2007 the federal Department of Health and Human Services, Office for Minority Health, collaborating with other federal agencies, sponsored the Indian Country Methamphetamine Initiative (ICMI). ICMI was undertaken to create community-driven, culture-based best practices in methamphetamine prevention and treatment which could then be disseminated throughout Indian Country. The ICMI ultimately involved ten tribes and five national organizations. Each tribe established a coalition of community government, nongovernment agencies, and elements of civic society to develop a comprehensive assessment, plan, and then to implement the plan. Each tribal coalition planned a complex array of activities including treatment programs, public education and mobilization, law enforcement strategies, and other intervention strategies, each intervention described within a logic model. These interventions focused on logic modeling; coalitions; capacity development and service system optimization; law enforcement and justice; individual and family treatment; public information, awareness, and education; community mobilization; and a very popular ICMI strategy, cultural renaissance. It was concluded that worthwhile activities were conducted under ICMI sponsorship, but that the specific aim of demonstrating community-driven, culture-based innovations in a manner suitable for dissemination was achieved only to a limited extent. Based on this outcome together with similar experiences, recommendations for future initiatives are suggested.