Patients with type 2 diabetes mellitus die of cardiovascular disease (CVD) at rates 2-4 times higher than patients without diabetes but with similar demographic characteristics. The prevalence of diabetes is increasing in the United States and, thus, the prevention of CVD in patients with diabetes poses an urgent public health challenge. The objective of this report is to review the current knowledge base for the prevention of CVD in patients with diabetes, with particular emphasis on the control of glycemia, lipids, and blood pressure. Epidemiologic analyses suggest that each 1% increase in glycosylated hemoglobin increases the risk for CVD by approximately 18%; however, evidence from the randomized trials that have examined whether glucose lowering reduces this risk is conflicting. Randomized trials have shown that lowering low-density lipoprotein cholesterol reduces CVD event rates by 17%-43% in patients with diabetes. Limited data support a role for lowering triglycerides and increasing high-density lipoprotein cholesterol in the prevention of CVD. Evidence from clinical trials shows that reducing systolic blood pressure to <140 mm Hg results in 30%-60% reductions in CVD events; however, epidemiologic evidence suggests that lowering to optimal systolic blood pressure levels (<120 mm Hg) may be additionally beneficial. Important questions regarding prevention of CVD in patients with diabetes remain unresolved, including the benefits of near-normal glycemic control, comprehensive therapy for diabetes-related dyslipidemia, and optimal blood pressure control. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial will test hypotheses to address these unanswered questions.