Patients with type 2 diabetes mellitus (T2DM) have an increased risk of incident and recurrent cardiovascular events including coronary, cerebrovascular, and peripheral arterial ischemia. For over 25 years, there has been rigorous study and provocative demonstration that lowering low-density lipoprotein cholesterol with a potent statin, and platelet inhibition with aspirin therapy, can reduce recurrent cardiovascular risk in these patients. T2DM patients with additional cardiovascular risk factors are at high risk for incident ischemic events and statin therapy is also efficacious in this setting. As a result, there has been widespread clinical implementation of statin therapy in patients with T2DM. In contrast, the additional benefit of aspirin therapy in patients without established cardiovascular disease, even those with T2DM, awaits definitive results. One important arena in which decisions and strategies for implementation of these therapies are crucial is within cardiovascular outcomes trials studying new therapies in patients with T2DM. A tested novel cardioprotective therapy is likely to be judged in the context of the trial patients' background treatment. In this review, we provide the data in support of, and our recommendations for, the use of statins and aspirin for the prevention of cardiovascular (CV) events in high-risk patients with T2DM. Current guidelines separate patients into those with either established cardiovascular disease (secondary prevention) and those patients at high-risk for cardiovascular disease as a result of multiple risk factors (primary prevention) when discussing the evidence for these cardiovascular preventive therapies, and we discuss these therapies in that context. In particular, we review the role of statins and aspirin for primary prevention therapy in high-risk patients with diabetes, considering recent results, potential controversy, and misconceptions of the benefits and risks of these medications in diabetic patients without a prior cardiovascular event.1–3 We conclude with a summary of the landscape of background therapy in contemporary cardiovascular outcomes trials of patients with T2DM, including trial recommendations for statin and aspirin treatment, highlighting the large ongoing SAVOR-TIMI 53 trial as an example.