Diabetes treatment should include drugs with absolutely no adverse effects toward cardiovascular risk. Indeed, it would be advisable to use drugs with intrinsic protective effect against the risk of cardiovascular events. Intervention trials aiming at demonstrating a protective cardiovascular effect of very tight glucose control have produced controversial results. It is commonly perceived, however, that early intervention with safe treatment strategies is likely to be beneficial. In regard to safety, in the attempt to firmly establish cardiovascular safety of new drugs for diabetes, Government Authorities have mandated that cardiovascular safety trials need to be performed for all new drugs registered for diabetes treatment. Several of such trials have already been performed and their results are available. These results support the cardiovascular safety of three dipeptidyl peptidase-4 inhibitors (sitagliptin, saxagliptin and alogliptin) and of a glucagon-like peptide-1 receptor agonist (GLP-1RA) (lixisenatide). These results, however, also document a plausible protective effect against cardiovascular risk associated with the use of a SGLT2 inhibitor (empagliflozin) and of two GLP-1RAs (liraglutide and semaglutide). Differences and similarities among the results of these cardiovascular safety trials as well as their potential implications will be discussed in this article.