This article systematically reviews 91 smoking cessation and tobacco prevention studies tailored for Indigenous populations around the world, with a particular focus on Aboriginal and Torres Strait Islander populations in Australia. We identified several components of effective interventions, including the use of multifaceted programs that simultaneously address the behavioural, psychological and biochemical aspects of addiction, using resources culturally tailored for the needs of individual Indigenous populations. Pharmacotherapy for smoking cessation was effective when combined with culturally tailored behavioural interventions and health professional support, though it is generally underused in clinical practice. From a policy perspective, interventions of greater intensity, with more components, were more likely to be effective than those of lower intensity and shorter duration. For any new policy it is important to consider community capacity building, development of knowledge, and sustainability of the policy beyond guided implementation. Future research should address how the intervention can be supported into standard practice, policy, or translation into the front-line of clinical care. Investigations are also required to determine the efficacy of emerging therapies (such as e-cigarettes and the use of social media to tackle youth smoking), and under-researched interventions that hold promise based on non-Indigenous studies, such as the use of Champix. We conclude that more methodologically rigorous investigations are required to determine components of the less-successful interventions to aid future policy, practice and research initiatives.