Systolic hypertension with or without diastolic hypertension is a major problem in hemodialysis (HD) patients; isolated diastolic hypertension is uncommon. Accelerated age-related changes in vascular stiffness, together with factors peculiar to uremia, lead to loss of large and small vessel distensibility and profound changes in circulatory function that includes an increase in systolic pressure and widening of the pulse pressure. Epidemiologic studies show a direct relationship of mortality with systolic blood pressure (BP) and an inverse relationship with diastolic BP. Thus systolic BP should be the focus of treatment. In HD patients with systolic hypertension, diastolic BP is inversely related to cardiovascular risk. An accurate diagnosis of hypertension followed by nonpharmacologic measures (sodium restriction, exercise, dry weight) should be the initial steps in BP reduction. The second step should be the use of antihypertensive agents, particularly the use of angiotensin converting enzyme (ACE) inhibitors and/or beta-blockers. The use of these agents has been associated with better outcomes in observational studies in HD patients. Furthermore, the administration of atenolol and lisinopril can be supervised three times a week to achieve improved BP control. Daily dialysis may improve BP and cardiovascular risk factors. Although more difficult to implement, it may emerge as a feasible alternative to conventional dialysis. Adequate systolic BP control with these available and emerging techniques should help stem the tide of cardiovascular mortality and mortality in HD patients.