With diabetes mellitus reaching epidemic proportions, mainly secondary to obesity, the impact of cardiovascular disease due to this combination makes it a dominant public health problem during the first quarter of the 21 st century. The complex interaction that results in diabetic heart disease is created by overlapping mechanisms. There is a propensity to develop premature,diffuse atherosclerotic coronary disease, which is associated with adverse short- and long-term morbidity and mortality. There are structural and functional abnormalities of the microvasculature, autonomic dysfunction, and intrinsic failure of myocardial contraction (so-called diabetic cardiomyopathy). These changes are amplified by arterial hypertension and kidney disease. In this review, we consider the role of the reninangiotensin-aldosterone system and how it is a crucial driver of most of the pathophysiologic mechanisms behind diabetic heart disease and why in the past 5 years blocking this system in diabetic patients has emerged as a critical therapeutic intervention.