Severe forms of hypertension demand treatment because they have a high incidence of morbidity and mortality that can be reduced by antihypertensive therapy. Stage 1-2 hypertension has a low morbidity and mortality; short-term benefits of treatment are harder to document. Managed care organizations know that members have a high turnover rate, so they are less interested in costly mass treatment to prevent a few future events. Stage 1-2 hypertension causes the vast majority of morbid events simply because a low incidence in a large population exceeds the lower absolute number of events in a small population with a high incidence. We must focus our efforts and resources on hypertensives at highest risk and thereby reduce the number needed to treat for 5 years (NNT) to avoid a morbid event. Obvious risks include hypertension severity, existing target organ damage, and concomitant diseases. Clues to the genetic etiology of primary hypertension are less obvious. DD genotype for angiotensin-converting enzyme (ACE) is associated with more left ventricular hypertrophy and greater risk for cardiovascular morbid events. Some genotypes of nitric oxide synthetase are associated with less effective production of NO and achieve less arterial vasodilation in response to stimuli. Many receptors have mutations that make them more or less functionally appropriate. Understanding these genetic factors may permit us in the future to focus appropriate drug therapy on the population most likely to benefit, thereby reducing NNT.