ISSUE ADDRESSED: There are no systematic reviews available to guide the delivery of programs to prevent or address substance misuse among young Indigenous Australians METHODS: A search was conducted for peer-reviewed journal articles published between 1990 and 2011 that evaluated interventions targeting young Indigenous Australians (aged 8-25 years) with the primary aim of reducing substance use. A comprehensive search was conducted of electronic databases (Cochrane, DRUG, Embase, Informit, Medline, Nursing and Allied Health, PreMedline and PsychInfo). Retrieved manuscripts were analysed using a narrative synthesis methodology. RESULTS: Eight published studies were found. Nearly all had major methodological limitations. Of the four projects that reported reductions in substance use, two included recreational or cultural activities and had strong community support, and one included supply control combined with employment opportunities. Two programs that provided education alone did not show changes in substance use. CONCLUSIONS: Increased systematic evaluation of efforts to prevent and treat substance use among young Indigenous Australians is needed. So what? The limited data support multiprong interventions, designed with community input, to protect young Indigenous people against substance misuse, rather than simple facts-based education. However, more research is needed.