Hypertension is commonly associated and acts synergistically with diabetes in increasing the risk of macrovascular and microvascular diabetic complications. Large-scale clinical trials have demonstrated that this risk is significantly reduced by intensive antihypertensive treatment, and accordingly, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guideline has further lowered the blood pressure goals for diabetic subjects to <130/80 mm Hg. This implies that most diabetic patients will require the combination of two or more antihypertensive agents to achieve this blood pressure target. Although the most effective combination strategy in diabetes has not yet been determined in large-scale randomized clinical trials, a combination that includes at least one agent that interrupts the renin-angiotensin system appears to not only have a good safety profile, but may also provide additional renal and cardiovascular protection. Other antihypertensive agents should be added based on the patients risk profile and overall treatment regimen to achieve blood pressure goal.