Prevalence of isolated systolic hypertension increases with age, due to progressive elevation of SBP, and is a major risk factor for cardiovascular morbidity and mortality. Extensive research has shown that lowering SBP improves cardiovascular outcomes in patients with isolated systolic hypertension, yet SBP control rates remain largely inadequate regardless of antihypertensive treatment. Arterial stiffness is a major determinant of elevated SBP resulting from structural changes in the vascular system, mediated by neurohormonal alterations that occur with vascular ageing. Clinical data have demonstrated an independent association between arterial stiffness and cardiovascular outcomes. Therefore, arterial stiffness has the potential to be an important therapeutic target in the management of isolated systolic hypertension. Current antihypertensive treatments have limited effects on arterial stiffness, so the development of new treatments addressing neurohormonal alterations central to vascular ageing is important. Such therapies may represent effective strategies in the future management of SBP.