The major cause of death and complications in patients with type 2 diabetes is cardiovascular disease. Cardiovascular complications that are often associated with diabetes include heart failure, acute myocardial infarction (MI), peripheral vascular disease, and cerebrovascular disease. More than 60% of all patients with type 2 diabetes die of cardiovascular disease, and an even greater percentage have serious complications. The impact of glucose lowering on cardiovascular complications is a hotly debated issue and recent large clinical trials, the Action in Diabetes and Vascular Disease (ADVANCE), Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Veterans Affairs Diabetes Trial (VADT) reported no significant decrease in cardiovascular events with intensive glucose control. Risk remains high even after correcting diabetes-associated dyslipidemia (high triglycerides and low HDL). Several mechanisms are likely to contribute to the accelerated atherosclerosis and increased cardiovascular disease risk seen in type 2 diabetics. Of these, postprandial hyperglycemia/lipemia, insulin resistance and inflammation may be the most important and under controlled contributing factors to vascular disease. The goal of this thematic issue is to address limitations of current therapies and review emerging research and therapeutic approaches that target inflammation, insulin resistance and other pathological mechanisms that contribute to cardiovascular disease in diabetes.