Individuals with diabetes are at high risk of cardiovascular (CV) disease, a risk that is significantly greater in the presence of traditional CV risk factors (hyperlipidaemia, hypertension, prothrombotic state). Glucose control and management of these risk factors decreases but does not eliminate CV events, reflecting the complexity of atherosclerosis. Novel risk factors (C-reactive protein, lipoprotein a, homocysteine, and endothelial dysfunction) have been proposed and are potentially modifiable. However, clinical trials data are not yet available to guide therapy. At this time, no single agent can achieve adequate risk reduction in patients with diabetes. Even with the use of multiple agents and classes of agents to manage CV risk, 75% of patients with diabetes are expected to die from CV causes. Despite the recent advances in primary and secondary prevention of CV events, new approaches are needed. Data from the Heart Outcomes Prevention Evaluation (HOPE) trial demonstrated that CV risk can be further reduced by the addition of the ACE inhibitor ramipril to the existing treatment regimen of high-risk patients with diabetes.