Tobacco use in Indigenous populations (people who have inhabited a country for thousands of years) is often double that of the non-Indigenous population. A disproportionate burden of substance-related morbidity and mortality exists as a result. To evaluate the effectiveness of smoking cessation interventions in Indigenous populations and to summarise these approaches for future cessation programmes and research. The Cochrane Tobacco Addiction Group Specialised Register of Trials was searched (April 2011), with additional searches of MEDLINE (May 2011). Online clinical trial databases and publication references were also searched for potential studies. We included randomized and non-randomized controlled trials for smoking cessation interventions in Indigenous populations. Interventions could include pharmacotherapies, cognitive and behavioural therapies, alternative therapies, public policy and combination therapies. No attempts were made to re-define Indigenous status for the purpose of including a study in this review. Data pertaining to methodology, participants, interventions and outcomes were extracted by one reviewer and checked by a second, whilst methodological quality was extracted independently by two reviewers. Studies were assessed by qualitative narrative synthesis and where possible meta-analysis. The review process was examined by an Indigenous (Aboriginal) Australian for applicability, acceptability and content. Four studies met all of the eligibility criteria for inclusion within the review. Two used combination therapies consisting of a pharmacotherapy combined with cognitive and behavioural therapies, whilst the remaining two used cognitive and behavioural therapy through counselling, one via text message support and the other delivered via clinic doctors trained in smoking cessation techniques. Smoking cessation data were pooled across all studies producing a statistically and clinically significant effect in favour of the intervention (risk ratio 1.43, 95%CI 1.03 to 1.98, p=0.032), however following sensitivity analysis a statistically non-significant but clinically significant effect was observed in favour of the intervention (risk ratio 1.33, 95%CI 0.95 to 1.85, p=NS) . A significant health disparity exists, whereby Indigenous populations, a minority, are over-represented in the burden of smoking-related morbidity and mortality. This review highlights the paucity of evidence available to evaluate the effectiveness of smoking cessation interventions, despite the known success of these interventions in non-Indigenous populations. Due to this lack of published investigations, the external validity of this review is limited, as is the ability to draw reliable conclusions from the results. The limited but available evidence reported does indicate that smoking cessation interventions specifically targeted at Indigenous populations can produce smoking abstinence. However this evidence base is not strong with a small number of methodologically sound trials investigating these interventions. More rigorous trials are now required to assist in bridging the gap between tobacco related health disparities in Indigenous and non-Indigenous populations.