The relationship between obesity and type 2 diabetes has been known for decades and the recent important increase in such diseases represents a major medical problem worldwide. Several prospective studies present both impaired insulin release and insulin resistance as the major factors for the development of type 2 diabetes. The factor that dominates in obesity is the permanent elevation of plasma FFA and the predominant utilization of lipids by the muscle inducing a diminution of glucose uptake and, therefore, insulin resistance. The rise in insulin secretion appears to be a compensatory mechanism that responds to the increased levels of circulating glucose. The fall in insulin secretion occurs as a late phenomenon. The present review aims at analysing the mechanisms that lead human obesity to type 2 diabetes and using the pathophysiological information for the prevention of diabetes. The partial reversibility of the evolution of obesity towards diabetes is well demonstrated today by lifestyle changes and multidisciplinary weight loss programs.