Cardiovascular diseases are major killers in all developed societies and rapidly becoming the leading cause of morbidity and mortality in the developing world. Patients with diabetes mellitus are at particular risk of developing cardiovascular diseases. The present treatment options for management of diabetes have expanded since the development of glucagon-like peptide-1 agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. There is a growing body of evidence that these agents may have cardioprotective effects even in patients who do not have diabetes. Here, we discuss this evidence as well as pathways that DPP-4 inhibitors target in the cardiovascular system. These agents over time will find an appropriate place in the management of cardiovascular diseases.