Background: Hypertension and type 2 diabetes mellitus (DM) frequently occur together, and their coexistence markedly enhances the risk for cardiovascular and renal disease. Each plays an important role in the metabolic syndrome, in which insulin resistance and compensatory hyperinsulinemia are features of both diseases. Objective: This article discusses the loss of hormonal homeostasis due to insulin resistance and the relationships among the triad of hypertension, type 2 DM, and cardiovascular disease. Methods: An online PubMed database search of articles published from 1994 to 2005 was conducted using search terms that included hypertension, type 2 DM, and cardiovascular disease. Relevant articles were studied and summarized in combination with the existing knowledge and expertise of the authors. Results: There is increasing evidence that the renin-angiotensin-aldosterone system is activated at the local-tissue level in patients with type 2 DM, as a result of insulin resistance, glucotoxicity, and other metabolic abnormalities. The common fertile soil of insulin resistance and lost hormonal homeostasis (genetic and environmentally driven) links these two entities. Multiple metabolic toxicities contribute to the strong association of an underlying oxidative-redox stress and reactive oxygen species, resulting in endothelial dysfunction and microalbuminuria. Because microalbuminuria is a precursor to cardiovascular disease, stroke, and chronic renal disease, it is important to screen for its presence in each patient with hypertension and type 2 DM. Conclusions: Renin-angiotensin-aldosterone system blockade is the cornerstone in managing these abnormalities; however, in type 2 DM, the angiotensin-converting enzyme inhibitors and/or the angiotensin receptor blockers seldom control the elevated blood pressure when used as monotherapy. Therefore, combination therapy with ≥2 antihypertensive agents, including thiazide diuretics, β-blockers, and calcium channel blockers, is required to reach the established blood pressure goal of <130/80 mm Hg. Careful control of hypertension in patients with type 2 DM decreases the morbidity and mortality resulting from cardiovascular and renal disease.