Insulin resistance, diabetes mellitus, and hypertension are associated with significant cardiovascula: morbidity and mortality. Lifestyle modifications effectively decrease the risk of progression to diabetes in high-risk patients, but intensive interventions can be costly and difficult for patients to maintain. The addition of pharmacotherapy is often necessary to treat hyperglycemia and hypertension and lower the risk of cardiovascular complications. Clinical trial data suggest the use of insulin-sensitizing and antihyperglycemic agents to delay the progression to diabetes. Similarly, analysis of data from clinical trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers indicate that the use of these agents results in fewer cases of new-onset diabetes among patients with hypertension, when compared with other antihypertensive agents. Angiotensin II has direct and indirect effects on insulin and its signaling pathways, providing support for the biologic mechanism underlying the benefits of renin-angiotensin system inhibition in preventing diabetes and cardiovascular events. Clinical trials now under way will further evaluate the role of renin-angiotensin system inhibition in preventing diabetes and its microvascular and macrovascular complications.