Hypertension is associated with damage to the heart, kidneys, and vascular tree. Assessment of target organ damage (TOD) allows better prediction of cardiovascular risk than conventional risk assessment. Regression of TOD during antihypertensive treatment, which depends on the blood pressure (BP) reduction and the specific ancillary properties of each drug, may indirectly indicate that BP is well controlled. It is unclear whether regression of TOD during treatment is associated with favorable outcome and should be used as a surrogate endpoint. There is evidence that regression of left ventricular hypertrophy and albuminuria are associated with a favorable outcome. However, recent studies cast doubts on this evidence. Thus, assessment of TOD is important to define cardiovascular risk, but, so far, regression of TOD cannot be regarded as a major surrogate therapeutic target. The present paper will provide a critical overview of the data available in the literature.