Diabetes patients are at high risk for development of cardiovascular disease. The cardiovascular safety of antidiabetic medications is a concern. Incretin therapies, including glucagon-like peptide 1 receptor (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors, have recently been introduced to clinical practice and are widely used. Data from phase 2 and 3 trials and retrospective analyses of clinical databases have shown favorable changes in cardiovascular risk factors and outcomes. However, only a few prospective trials have been designed with cardiovascular outcomes as a primary end point. From current data, alogliptin and saxagliptin do not change cardiovascular risk in type 2 diabetes mellitus (T2DM) patients. Vildagliptin does not alter myocardial function in T2DM patients with systolic dysfunction. However, the possibility of an increase in clinical heart failure and worsened outcomes in patients with existing heart failure is suggested by current data. Clinicians need to follow patients on DPP-4 inhibitors carefully for this possibility until more prospective randomized controlled data are available.