This review article presents data to show that insulin resistance and diabetes mellitus are conditions associated with low-grade inflammation. It shows that inflammation pre-dates the detection of diabetes and predicts its occurrence. Furthermore, it discusses the inter-relationship between inflammation associated with insulin resistance and diabetes, and the inflammation associated with atherosclerosis, the main complication of insulin resistance and diabetes. These data provide a new paradigm for understanding how insulin resistance, diabetes, and cardiovascular disease are related to one another. This paradigm also has the potential for opening up new areas of research and treatment.