Effective drug treatment of hypertension for the prevention of fatal and nonfatal cardiovascular disease passed its 50th anniversary 2 years ago.1 Until recently, the most consistent observation among trials had been that stroke risk was directly related to the fall in blood pressure on treatment.2 Older trials established the value of antihypertensive drug treatment and generally recruited disease-free participants at their outset. Recent trials have focused on less healthy participants. Recruitment has been extended to those with a prior stroke, recent myocardial infarction, coronary artery disease, chronic renal disease (with or without diabetes mellitus), heart failure, and combined high-risk states and the elderly (old-old). The benefit of antihypertensive drug treatment is still related to the reduction in blood pressure.3 Differences between drug classes have been found in some but not all trials; the differences are generally small, even if statistically significant. Antihypertensive drug treatment is effective in reducing risk for those with a higher disease burden, but risk is never lowered to levels equal to those who have lower pressure without antihypertensive drug treatment and lack prior cardiovascular disease. The hands of the cardiovascular clock may slow, but they never stop or reverse. It is a challenge to unmask traits that might account for the limited effectiveness of antihypertensive drug treatment in its present form. Article see p 569 In a retrospective look at blood pressure patterns in several stroke trials and the Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering (ASCOT BP) …