Once considered an inconsequential part of the aging process, an age-associated rise in systolic blood pressure (SBP) occurs as a consequence of increased arterial stiffness and contributes to a high prevalence of systolic hypertension after middle-age. Elevated SBP imparts a predilection toward the onset of vascular events, highlighting the importance of its control. Current philosophy ranks systolic pressure as the most relevant component of blood pressure (BP) for determining risk for cardiovascular and other events in hypertensive patients, particularly those >50 years of age. Despite its prognostic role, SBP remains more difficult to control than diastolic BP (DBP), and most middle-age and older hypertensive patients fail to achieve recommended targets. In part, the lack of strict control of SBP in the more aged population lies in the physiology of hypertension. Younger persons tend toward isolated diastolic hypertension or combined systolic-diastolic hypertension, primarily driven by increased peripheral resistance and more effectively treated by antihypertensive medications; whereas older persons develop isolated systolic hypertension (ISH) associated with increased arterial stiffness that appears to be less amenable to current therapies. Thus, diastolic pressure in hypertensive patients often plateaus as patients reach middle-age and subsequently declines, whereas systolic pressure consistently rises through the ensuing decades. Treatment approaches favoring control of DBP frequently result in residual high SBP, putting patients at greater risk for vascular complications. Improving patient outcomes relies on antihypertensive therapy that appropriately addresses control of SBP and pulse pressure, underscoring the importance of therapeutic options that effectively reduce arterial stiffness.