The aim was to review the evidence for the long-term effects of weight loss on diabetes outcomes in obese people or for those at risk of developing type 2 diabetes. Current evidence is mostly based on short-term studies. This is a systematic review of long-term outcomes of weight loss in studies published between 1966 and 2001. Eleven long-term studies with a follow up of more than 2 years were included. Results show that those with diabetes who lost weight intentionally significantly reduced their mortality risks by 25%. Additionally, weight loss of 9–13 kg was most protective. Patients with the risk of developing diabetes due to either family history of diabetes or impaired glucose tolerance, saw a reduction in this risk. Those with large weight losses achievable with surgical interventions reduced their risk by at least 63%. Metabolic handling of glucose improved in 80% of those already with type 2 diabetes who lost weight. Based on one large study, intentional weight loss in obese patients appears to have a beneficial effect on mortality risk for those with type 2 diabetes. Clearly, further studies are needed to endorse this. The risk of developing diabetes being reduced by weight loss was shown in seven studies. However, the results were from studies with different analytical adjustments and outcome indices, making it difficult to make direct comparisons and should be viewed with caution. More long-term prospective studies need to be conducted with commitment to improving the methodological quality and standardization, in order to accurately assess the long-term effects of weight loss for obese diabetic and non-diabetic individuals.