Diabetes mellitus (DM) has already affected one in every eleven person in the global population, and the dis-ease prevalence continues to increase because of the obesity pandemic. Even with the availability of a multitude of antidi-abetic medications for optimal glycaemic control, cardiovascular morbidity and mortality were not largely altered until re-cently when newer antidiabetic drugs such as glucagon-like peptide-1 receptor analogues (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors were introduced. Cardiovascular safety of antidiabetic drugs has also been a hot topic for global scientific debate after the US Food and Drug Administration (FDA) enforced restrictions on Rosiglita-zone in 2010 with the suspicion of increased mortality and myocardial events (with subsequent uplift of the ban on the drug in 2013 following the emergence of additional evidence on safety). After this debate, all antidiabetic should go through rigorous safety checks with cardiovascular outcome trials (CVOTs). Recent CVOTs with GLP-1RAs and SGLT2 inhibitors have revealed markedly positive outcomes that have changed the landscape of diabetes management across the world. Thus, the therapeutic algorithm for optimal management of DM should consider not only the glycaemic control ef-ficacy of the individual antidiabetic agent but also the cardiovascular safety and modifications in other anticipated long-term DM complication profiles. Therefore, it is imperative to critically appraise the efficacy and cardiovascular safety of all antidiabetic drugs to improve the scientific practice of our diabetes care globally. This issue, “Efficacy and cardiovas-cular safety of antidiabetic medications,” provides readers the back-up of up to date evidence.