Cardiovascular diseases (CVDs) are the major causes of morbidity and mortality in persons with diabetes, and many factors, including hypertension, contribute to this high prevalence of macrovascular complications. Hypertension is approximately twice as frequent in subjects with diabetes compared with non-diabetic patients. Furthermore, up to 75Y% of CVD in diabetes may be attributable to hypertension, leading to recommendations for more aggressive treatment (i.e. reducing blood pressure to < 130/80 mmHg) in persons with coexistent diabetes and hypertension. Macroangiopathy in diabetes is manifested by accelerated atherosclerosis which affects heart, brain and peripheral arteries. The pathogenesis of this accelerated atherosclerosis is multifactorial and includes a very complex interaction. Several data suggest a key role for renin-angiotensin system (RAS) activation in the pathophysiology of macrovascular complications in diabetic hypertensive subjects. Consequently, RAS blockade exerts potent antiatherosclerotic effects, which are mediated by their antihypertensive, anti-inflammatory, antiproliferative, and oxidative stress lowering properties. Inhibitors of the system, ie, angiotensin converting enzyme inhibitors and angiotensin receptor blockers, are now first line treatment to prevent CVD in patients with diabetes and hypertension. In addition, recent clinical trials have suggested that RAS blockade may protect against the development of de-novo diabetes in at-risk patients. Finally, the recent identification of new components of the RAS should provide fertile territory to not only examine new targets linked to the RAS but potentially to design more rational treatments for the prevention of CVD in patients with diabetes and hypertension.