The adverse cardiovascular consequences of high blood pressure (BP) not only depend on absolute BP values, but also on BP variability (BPV). Evidence has been provided that independently of mean BP levels, BP variations in the short- and long-term are associated with the development, progression and severity of cardiac, vascular and renal organ damage, and with an increased risk of CV events and mortality. Alterations in BPV have also been shown to be predictive of the development and progression of renal damage, which is of relevance if considering that impaired renal function in a hypertensive patient constitutes a very potent predictor of future CV events and mortality even in treated subjects. This review will address whether antihypertensive treatment should target alterations in BPV, in addition to reducing absolute BP levels, in order to achieve the highest CV and renal protection in hypertensive and renal patients.