Introduction: The purpose of this paper is to review evidence relating to ‘what works’ to influence the social and economic determinants of Indigenous health, in order to reduce health inequities, and ultimately contribute to closing the life expectancy gap between Indigenous and non-Indigenous Australians. We outline a conceptual framework for understanding how social and economic determinants influence health and wellbeing, and identify a number of key determinants of health. We review evidence relating to how each determinant is associated with Indigenous health and wellbeing, and then consider specific actions designed to improve Indigenous outcomes in each of these areas in order to determine the characteristics of successful initiatives. Based on our conceptual framework, we link successful actions which result in positive outcomes for Indigenous Australians in each of the key determinants to ultimately improving health and wellbeing and contributing towards ‘closing the gap’ in health and wellbeing. We note that many actions we consider only aim to improve the situation for Indigenous Australians in regard to that specific area (for example, education, housing) and were not devised to take direct action to improve health, even though the evidence indicates that those actions may be likely to contribute to improved health over the longer term.