Despite the strong association between hypertension and accelerated atherosclerosis, and the known beneficial clinical effects of beta-blockers in patients with coronary artery disease, antihypertensive trials of beta-blockers have shown only modest protection against fatal and nonfatal myocardial infarction. This review explores the explanations put forth for this apparent failure of beta-blockers. It also examines the clinical relevance of the metabolic effects of beta-blockers within the framework of the heterogeneity of this class of drugs. Recent evidence indicates that long-term treatment of hypertension with beta-blockers that do not possess intrinsic sympathomimetic activity reduces the occurrence of cardiac complications of hypertension. There are no data to show a quantified effect on clinical outcome of the lipid and glucose changes associated with beta-blocker therapy. The metabolic influence of these drugs varies considerably within the class and may be of little clinical relevance. Unless it is contraindicated, an appropriate beta-blocker should be considered for the treatment of hypertension in patients who have coronary artery disease or who are at high risk for coronary artery disease.