High rates of substance use and related problems have been long recognized as critical health issues for Native American adolescents. Unfortunately, no manualized interventions address the specific needs of Native American adolescents in a culturally appropriate manner. In 2006, the Cherokee Nation partnered with the University of Colorado to employ a community-based participatory research process to develop an intervention for Native American adolescents with substance use problems. The resulting intervention, Walking On, is an explicit blend of traditional Cherokee healing and spirituality with science-based practices such as cognitive behavioral therapy and contingency management and is designed to address the specific needs and worldviews of Native American adolescents with substance use problems and their families. Each individual and family session includes a brief assessment, a skill-building component, and a ceremony. A Weekly Circle (multifamily group) promotes sobriety and builds a community of healing. Early pilot study results suggest that Walking On is feasible for use in tribal substance abuse treatment programs. While Walking On shows early promise, the intervention will require further study to examine its efficacy.