Diabetes is an ancient disease and for centuries extreme diets and herbal remedies were used to treat diabetes symptoms. The discovery of insulin in 1921 transformed the landscape of diabetes treatment and was followed by the discovery of several new therapies which improved glycemia and increased patient life span. However, as patients with diabetes lived longer, they developed classic microvascular and macrovascular diabetes complications. In the 1990s, the DCCT and the UKPDS trials demonstrated that tight glucose control reduced the microvascular complications of diabetes, but had marginal effects on cardiovascular disease, the leading cause of death in patients with diabetes. In 2008, the FDA directed that all new diabetes medications demonstrate cardiovascular safety. From this recommendation emerged novel therapeutic classes, the GLP-1 receptor agonists and SGLT2-Inhibitors, which not only improve glycemia, but also provide robust cardio-renal protection. In parallel, developments in diabetes technology like continuous glucose monitoring systems, insulin pumps, telemedicine and precision medicine have advanced diabetes management. Remarkably, a century later, insulin remains a cornerstone of diabetes treatment. Also, diet and physical activity remain important components of any diabetes treatment. Today type 2 diabetes is preventable and long-term remission of diabetes is possible. Finally, progress continues in the field of islet transplantation, perhaps the ultimate frontier in diabetes management