Macrovasculature, microvasculature, and the heart determine the structure and function of the circulatory system. Due to the viscoelastic properties of large arteries, the pulsatile pressure and flow that result from intermittent ventricular ejection is smoothed out, so that microvasculature mediates steadily the delivery of nutrients and oxygen to tissues. The disruption of this function, which occurs when microvascular structural alterations develop in response to hypertension, leads to end-organ damage. Microvascular structure is not only the site of vascular resistance but also the origin of most of the wave reflections that generate an increased central systolic blood pressure. The presence of structural alterations in the small resistance arteries may be considered an important link between hypertension and ischemic heart disease, heart failure, cerebral ischemic attacks and renal failure. An increased arterial wall thickness together with a reduced lumen may play an important role in the increase of vascular resistance, and may also be an adaptive response to the increased haemodynamic load. The increased media to lumen ratio is also a powerful predictor of subsequent cardiovascular events. In addition, essential hypertension seems to be associated with a rarefaction of arterioles and capillaries. Nowadays many data of the literature suggest that hypertension-related damage to the micro and macrovascular system may be manageable through pharmacological agents. Among them, beta-blocking agents and diuretics have never modified the microvascular structure, whereas renin-angiotensin system antagonists and calcium entry blockers had an opposite effect being able of reversing structural alterations, thereby reducing central wave reflections and, finally, causing a selective systolic blood pressure reduction.