BACKGROUND: We systematically reviewed the published evidence for the developmental origins of health and disease hypothesis among aboriginal populations from Australia, Canada, New Zealand and the USA. METHODS: Medline, EMBASE and the Informit Health databases were systematically searched (March 2012) using medical subject headings and keywords for studies that examined the effect of prenatal factors and birth outcomes on later life (≥3 years) cardio-metabolic diseases. Quality of studies was independently assessed by two reviewers using a risk of bias assessment tool; main findings from studies with a low to moderate risk of bias were summarised qualitatively. RESULTS: In all, 844 studies were found; 50 were included in the review of which 41 had a low-moderate risk of bias. There was strong evidence for an association between birth weight and type 2 diabetes (6/7 studies), impaired kidney function (6/7 studies) and high blood pressure (5/6 studies), whereas there was limited evidence for an association with metabolic abnormalities (4/7 studies) and adiposity (4/7). Exposure to maternal diabetes was strongly associated with type 2 diabetes (9/10 studies) and metabolic abnormalities (5/7 studies), whereas the association with adiposity was low (3/9 studies); the limited number of studies, to date, also show a relationship with high blood pressure (2/2 studies). CONCLUSIONS: This review highlights that interventions to reduce the burden of cardio-metabolic disease among aboriginal populations should focus on improving maternal health, particularly by reducing the prevalence of diabetes in pregnancy. Future research should also be directed towards potential protective actions, such as breastfeeding.