Atherosclerosis and cardiovascular disease are the major causes of morbidity and mortality in patients with diabetes and those with insulin resistance and the metabolic syndrome. Both conditions profoundly accelerate the development of atherosclerosis and increase the morbidity and mortality of cardiovascular events. The question, therefore, is what are the molecular/biochemical mechanisms that underlie the potentiating influence of diabetes, the metabolic syndrome and/or insulin resistance on the development and progression of atherosclerosis? The following review will focus on the molecular mechanism whereby hyperglycaemia and/or hyperinsulinemia either directly or indirectly promote atherosclerosis.