The major antihypertensive drug classes appear to exert differing effects on glycemic control and diabetes incidence. Thiazide diuretic and β-blockers are potentially diabetogenic, whereas calcium channel blockers appear neutral. Inhibitors of the renin-angiotensin system are associated with improvements in glycemic control and may lower diabetes incidence, but it is not clear if this represents a truly preventive effect. Also, it should be noted that previous studies have reported inconsistent results, and the data to date are not definitive. We suggest that inhibitors of the renin-angiotensin system be used as first-line agents in uncomplicated hypertensive patients who are at high risk for developing type 2 diabetes. Thiazides and β-blockers should not be avoided in patients with compelling indications for these drugs. Many hypertensive patients (particularly those who are obese or have prediabetes) require several agents to achieve target blood pressure levels. Therefore, the choice of initial agent is far less important than ensuring that target blood pressure goals are reached.