Vital organs are exposed to the central rather than the brachial blood pressure. To date, central blood pressure can be assessed noninvasively through the use of several devices. In this review, we critically discuss the clinical relevance of central blood pressure assessment. Considerable evidence suggests that central blood pressure is a better predictor of end-organ damage than brachial blood pressure. However, there is still uncertainty concerning the value of central pressure for predicting cardiovascular outcomes, as the existing studies are underpowered to address this issue. A full synthesis of the available data is needed in this regard. Among the different antihypertensive drug classes, beta-blockers appear to lower central blood pressure less than brachial blood pressure. This difference may, at least in part, explain the reduced efficacy of beta-blockers in the prevention of cardiovascular outcomes compared with the other antihypertensive drug classes, which may lower central and brachial blood pressure to a similar extent. Nevertheless, this differential effect might not be relevant to the newer beta-blockers with vasodilating properties, including nebivolol, celliprolol and carvedilol. However, whether a preferential reduction of central blood pressure results in better outcomes should be further assessed by appropriately powered clinical trials. Other emerging challenges include the assessment of the potential predictive value of central blood pressure variability and the development of new antihypertensive medications based on central blood pressure rather than brachial blood pressure.