The calcium antagonists are effective in the treatment of essential hypertension. This quality, in addition to their ability to inhibit atherosclerotic lesion formation, may make them superior to other classes of antihypertensive agents in preventing vascular complications of mild to moderate hypertension. Preliminary results of clinical trials suggest that the calcium antagonists retard the progression of early atherosclerotic lesions in native coronary arteries and saphenous vein grafts, but have less effect on established lesions. Further study is needed to determine whether these agents have a favorable effect on the overall clinical outcome of patients with coronary artery disease. Clinical trials also suggest that the calcium antagonists retard the progression of renal insufficiency in hypertensive patients by mechanism(s) that do not depend on blood pressure lowering per se. Prospective studies with larger numbers of patients are needed to determine whether these apparent renoprotective effects are sustained for the long term in both diabetic and nondiabetic hypertensive populations. The dihydropyridine calcium antagonists are effective in reducing brain damage and mortality secondary to acute ischemic stroke. It is still unknown whether they are also effective in the primary and secondary prevention of ischemic stroke, and whether other classes of calcium antagonists are useful in the prevention and/or treatment of ischemic stroke. The potential antiatherosclerotic and cardio-, neuro-, and renoprotective effects of the calcium antagonists, coupled with their lack of adverse metabolic effects, have defined an expanding therapeutic role for these agents in the 1990s. © 1991 by the American Journal of Hypertension, Inc.