Sustained activation of the sympathetic nervous system leads not only to elevated blood pressure but also to vascular remodeling, microvascular complications, and target organ damage. Although beta-blocking agents, which act directly on the adrenergic receptors of the sympathetic nervous system, have been used in the treatment of hypertension for almost 40 years, questions have recently arisen about their effectiveness as first-step treatment. Lack of consistent outcome data may relate to the failure of traditional beta-blockers (eg, atenolol, metoprolol, and propranolol) to positively affect peripheral vascular resistance; instead, these agents rely on reduction of cardiac output to lower blood pressure. Accumulating evidence points to reductions in vascular resistance as an important component in hypertension treatment, especially with regard to improving vascular remodeling and reducing target organ damage. The vasodilating beta-blockers carvedilol, labetalol, and nebivolol block beta-adrenergic receptors and vasodilate through diverse mechanisms, allowing for the possibility of better tolerability and adherence and translating into a more favorable effect on the vasculature compared with traditional beta-blockers.