In the past 2 decades, deaths from stroke have decreased by 59% and deaths from heart attack by 53%. An important component of this dramatic change has been the increased use of antihypertensive drugs. This remarkable success resulted from broad-based and diverse research programs supported by the federal government, pharmaceutical companies, voluntary health agencies, and private foundations. It included basic research, drug development programs, epidemiologic studies, health surveys of US citizens, clinical research, and large-scale drug trials. Four of the categories of antihypertensive drugs in wide use--diuretics, beta-blockers, calcium antagonists, and angiotensin-converting enzyme inhibitors--emerged from widely different areas of investigation. In the beginning, the major breakthroughs that led to the development of these drugs were impossible to forecast, and their ultimate applications were impossible to predict. Although decreases in hypertension-related mortality are impressive, enthusiasm must be tempered because the mechanisms of hypertension are still incompletely understood and prevention is not yet possible. Continued research is needed to extend these advances.