It is well established that in young and healthy individuals central (aortic or carotid) systolic and pulse pressures are different from peripheral (brachial) corresponding pressures as a consequence of progressive changes in arterial stiffness and pressure wave reflections along the arterial tree. There is evidence indicating that in interventions with pharmaceutical and non-pharmaceutical agents, central pressures are subjected to greater changes than peripheral pressures, and they are more closely related to the pathophysiology of end-organ damage or cardiovascular risk. Therefore central blood pressures may be of higher clinical importance than peripheral pressures. The present review aims to provide an insight into the (patho)physiology of central blood pressures, to present the most accurate techniques for their estimation, and to discuss the available experimental and epidemiological data that support the emerging need for the evaluation of central blood pressures in clinical practice.