The nature of the clinical problem posed by hypertension has been changed fundamentally by 30 years of successful drug therapy. Cardiovascular pathology directly related to the high pressure is no longer the main problem. Complications of atheroma, particularly in the coronary arteries, are the main cause of hypertension-related deaths. Most patients now starting treatment have mild hypertension and the benefits, although significant, are small (two deaths prevented per 1000 patient-years of treatment). These two considerations dictate that new drugs must have a very low incidence of toxicity, a low incidence of symptomatic side effects, and preferably, a favorable effect on morbidity and mortality from ischemic heart disease. Several possible approaches have promise: 1) reduction of ischemic heart disease mortality by beta-adrenergic blockade; 2) use of calcium entry blocking drugs, which may combine vasodilation with antiarrhythmic effects; 3) non-thiol-converting enzyme inhibitors, which may have a particularly low incidence of side effects; 4) prostanoid derivatives that may combine vasodilatation with an antiplatelet action.