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Hypertension frequently coexists with diabetes and the cardiometabolic syndrome. β-Blockers have been a mainstay for controlling blood pressure for nearly 4 decades. However, β-blockers are perceived to cause glucose and lipid metabolism dysregulation, including hypoglycemia masking, reduced glycemic control, insulin resistance, and dyslipidemia. It should be noted, however, that β-blockers are diverse in their effects on glucose and lipid metabolism. Potential mechanisms that contribute to these metabolic effects include hemodynamic differences, anti-inflammatory and anti-oxidative pathways, and/or weight changes. Traditional β-blockers decrease cardiac output while peripheral vascular resistance increases or remains unchanged, which may result in glucose and lipid abnormalities. In contrast, vasodilating β-blockers reduce peripheral vascular resistance but have little effect on cardiac output. Vasodilating β-blockers may therefore result in less impact on insulin sensitivity and glycemic control, a reduced new-onset diabetes risk, and improved dyslipidemia compared with traditional β-blockers. Because of these effects, vasodilating β-blockers may represent a favorable option in the treatment of high-risk patients with hypertension. J Clin Hypertens (Greenwich). 2011;13:52–59. ©2010 Wiley Periodicals, Inc.