Blood pressure (BP) fluctuations over time physiologically result from the complex interaction between environmental stimulation, genetic factors, and cardiovascular control mechanisms. Ambulatory BP-monitoring techniques, in particular systems providing beat-by-beat BP recording, have allowed a detailed description of the different components contributing to overall BP variability (BPV) over 24 hours, including short-lasting and more sustained BP changes. In hypertension, BPV increases with increasing BP levels, and evidence is available that its magnitude correlates closely with target-organ damage and with the incidence of cardiovascular events, independent of absolute BP levels. It has been suggested that drugs capable of providing smooth 24-hour BP control, reducing BPV, may confer additional target-organ protection. Mathematic indices, such as the trough-to-peak ratio and the smoothness index, represent useful measures of the homogeneity of the antihypertensive effect over 24 hours. Further studies are still needed to confirm that, in humans, interventions that can reduce BPV can also reduce the rate of cardiovascular events.