The occurrence of blood pressure fluctuations over time has been documented since the 18th century, but the clinical importance of this phenomenon is only now being recognized. The introduction of ambulatory blood pressure monitoring in the late 1960s represented a major step forward in the study of blood pressure behaviour and helped to characterize the relationship between blood pressure variability and cardiovascular disease. In hypertension, blood pressure variability increases with increasing blood pressure and correlates closely with target-organ damage, independently of absolute blood pressure values. This has important consequences for treatment, which in the past has focused on reducing mean blood pressure values as the main goal. Experimental evidence suggests that drugs capable of buffering or reducing blood pressure variability may confer additional benefits on target-organ protection. Effective target-organ protection could best be afforded by antihypertensive agents that provide efficient 24-h blood pressure control and also stabilize blood pressure variability. Mathematical indices, such as the trough:peak ratio and the smoothness index, provide useful measures of the homogeneity of the antihypertensive effect over 24 h; optimum control is provided by drugs with a trough:peak ratio close to 1 and a smoothness index > 1, as is observed with long-acting drugs such as telmisartan or amlodipine. Recently, a direct relationship was demonstrated between homogeneous blood pressure control and treatment-induced regression of left ventricular hypertrophy, emphasizing the importance of smooth 24-h blood pressure control. In conclusion, the goals of antihypertensive treatment should consider the reduction of both 24-h mean blood pressure and its variability. Long-lasting drugs or drug combinations are preferable to ensure a homogeneous and smooth 24-h blood pressure profile.