Epidemiological studies in the past decade have stressed the importance of pulse pressure (PP) as an independent risk factor for cardiovascular morbidity and mortality. We briefly review the epidemiological evidence and discuss the pathophysiological mechanisms which involve arterial stiffness and wave reflections in older patients. We discuss the therapeutic consequences of targeting PP rather than systolic (S) or diastolic (D) blood pressure (BP) when using antihypertensive agents. With this line of evidence it is important, first, to determine what minimal PP level indicates cardiovascular risk and, second, to note that an increasing number of clinical studies indicate that PP is poorly sensitive to placebo, while SBP and DBP are conversely highly sensitive. Finally, on the basis of large-scale intervention trials, PP seems to be an appropriate tool for studies of clinical pharmacology and therapeutics in the fields of hypertension, congestive heart failure and other cardiovascular diseases.