The blood pressure (BP) waveform varies substantially between the peripheral conduit (brachial) and the central elastic (aorta) arteries mainly do a gradual increase of systolic BP, as the wave propagates distally. This phenomenon is called BP amplification and is principally generated by the presence of arterial stiffness gradient and wave reflections along the arterial bed. More and more clinical studies suggest that central BP may provide additional information regarding cardiovascular risk beyond peripheral BP. Arterial properties and thus pressure amplification, are modulated by age, cardiovascular risk factors, vasoactive substances and drugs. Recent evidence suggests, beyond any doubt, that antihypertensive drugs affect peripheral and central BP differentially and alter pressure amplification. In the present review (Part I) we deal with the mechanisms underlying: (i) the genesis and recording of BP difference between central and peripheral arteries (pressure amplification), (ii) the rational of differential effect of antihypertensive drugs on pressure amplification, (iii) the pathophysiological role of pressure amplification on cardiovascular disease as well as its clinical and research implications.