Despite the considerable progress in our understanding of the mechanisms of hypertension-related cardiovascular damage, assessment of treatment benefit is so far based on randomized trials monitoring cardiovascular events only. There are inherent limitations to this approach. First, the mechanisms precipitating events are partly different from mechanisms leading to the underlying vascular injury, and evidence obtained on therapeutic prevention of events cannot be automatically applied to therapeutic prevention of disease. Second, event-based trials are suitable to test treatment effectiveness only in those conditions, such as severe hypertension and hypertension in the elderly, in which a high rate of events is expected during the necessarily short duration of the trials. Third, in young and middle-aged patients with mild hypertension, event-based trials are likely to have markedly underestimated treatment benefits. Fourth, in these patients the benefits of antihypertension therapy can be better explored by trials monitoring the progress of organ damage than by trials monitoring the occurrence of events. Finally, trials monitoring organ damage are now feasible as new quantitative, sensitive, and reliable techniques are available. Both prevention of cardiovascular events and prevention of organ damage and disease are essential goals of antihypertension therapy, and achievement of these two distinct goals has to be evaluated through trials using different types of criteria.