Although β-adrenoceptor antagonists (β-blockers) have effects on metabolism via their mechanism as blockers of adrenergic stimulation, most interest in the metabolic effects of β-blockers is caused by their effect on glucose metabolism. Strict metabolic control and management of cardiovascular risk factors in patients with diabetes mellitus has proven to be of great importance in the improvement of prognosis. β-Blockers are necessary tools for the treatment of heart failure and hypertension. The use of β-blockers in patients with diabetes mellitus has been controversial because of fear of deterioration of metabolic control of glucose and lipids and blunting of the symptoms of hypoglycemia. Currently, it appears that there is a beneficial metabolic effect with the third-generation β-blocker carvedilol. Comparisons have been made between the second-generation β-blocker metoprolol and carvedilol, with a clear advantage for carvedilol in terms of metabolic control. In the GEMINI (Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives) trial, a decrease of 9.1% (p = 0.004) in insulin resistance, compared with baseline values, was seen in patients treated with carvedilol, whereas no significant difference was seen in the group of patients treated with metoprolol. Additionally, an increase in glycosylated hemoglobin of 0.15% from baseline was seen in the metoprolol group (p < 0.001) compared with no significant change in the carvedilol group. These findings indicate that, as carvedilol exerts favorable effects on glucose metabolism compared with metoprolol, patients with diabetes mellitus could benefit from treatment with carvedilol rather than metoprolol. The mechanisms behind these findings are not yet fully understood. Several mechanisms have been suggested, and special interest has been paid to the investigation of the potential beneficial role of the β₂- and α₁-adrenoceptor-blocking effects of carvedilol, along with its known antioxidant properties.