Type 2 Diabetes continues to rise in prevalence throughout the globe, and cardiovascular diseases remain the most common cause of morbidity and mortality among patients. Dipeptidyl-peptidase-4 (DPP-4) inhibitors are a newer class of oral anti-hyperglycemic agents whose effect is mediated through the incretin hormones, GLP-1 and GIP. In this review, we discuss the incretin system, DPP-4 inhibitors and their mechanism of action and, principally, the potential impact of DPP-4 inhibition on the cardiovascular system. Some pre-clinical data, small mechanistic studies and post-hoc analyses of randomized clinical trials suggest a possible beneficial effect on cardiovascular risk. However, the relationship between DPP-4 inhibition and actual cardiovascular outcomes remains unknown. We therefore also review ongoing large, randomized clinical trials examining this very question.