Inhibitors of the sodium glucose transporter 2 (SGLT2) such as canagliflozin, dapagliflozin, or empagliflozin were primarily developed for the treatment of diabetes. Meanwhile, they have been game changers in the treatment of conditions such as heart failure and renal failure in both diabetic and non-diabetic patients. Importantly, they do not only improve disease-specific outcomes but even reduce overall mortality by about one third. Thus, they have become game changers for indications affecting millions of people. This volume discusses their efficacy and safety with emphasis on diabetes, heart failure and renal failure. Mechanistic insight from animal studies and potential additional uses are also being discussed.