Although the differences between central and peripheral BP (blood pressure) have been known for decades, the consequences of decision-making based on peripheral rather than central BP have only recently been recognized. The influence of cyclic stretch (owing to cyclic changes in BP) on the aortic wall in atherosclerosis has been documented at every stage of its development. Apart from mediating atherosclerosis progression and plaque instability, the pulsatile component of BP is the main mechanism leading to plaque rupture and, consequently, to acute coronary syndromes and other vascular complications. The principal goal of the present review is to evaluate the role of central BP measurements, principally systolic and pulse pressure, for cardiovascular risk assessment. Recent findings suggest that the pulsatile component of BP (when represented by central pulse pressure or central pulsatility) is one of the most important factors determining event-free survival. Results of several prospective studies (using both invasive and non-invasive measurements of central BP) indicate not only an independent predictive value of central pulse pressure, but also its advantage over brachial pressure. Recent evidence suggests that some antihypertensive drugs can influence central BP more consistently when compared with peripheral BP. This is especially true for agents acting on the renin-angiotensin system. Nevertheless, large prospective studies aiming at the comparison of the predictive value of peripheral and central BP in the general population, as well as studies comparing the effectiveness of hypertension management based on peripheral compared with central BP measurements, are needed before algorithms based on central BP can be recommended for clinical practice.