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Arterial aging is associated with a progressive increase in aortic stiffening, which results in a rise in central aortic pressures. Traditionally, blood pressure (BP)-lowering therapy has been directed at brachial rather than central pressures. However, a key contemporary question is whether this strategy is optimal in reducing aortic pressure and aortic stiffness, and whether specific treatment strategies might be preferred to reduce the process of arterial aging. This review examines current evidence that BP-lowering treatments can differentially affect aortic pressure and stiffness parameters relative to brachial BP. There is now unequivocal evidence that different treatment regimens can differentially affect BP in the central aorta relative to brachial BP, and emerging evidence of BP-independent differential drug effects on arterial stiffness. A remaining challenge is to link any potentially favorable changes in aortic pressure and/or stiffness to improvements in morbidity and mortality over and above those expected from conventional BP lowering.