SGLT2 inhibitors are molecules able to reduce blood glucose levels and body weight, and to lower systolic blood pressure. They also exert important diuretic and modulatory effects of renal hemodynamics, as well as a series of anti-inflammatory actions, thus contributing to reduce the cardiovascular burden in subjects with and without type 2 diabetes. Such benefit mainly translates into reduced risk for hospitalization due to heart failure, and reduced decline of glomerular filtration, associated with a powerful anti-albuminuric effect. For this reason, they constitute an indispensable treatment in a modern approach to cardiorenal prevention. This review recapitulates the clinical evidence supporting the use of SGLT2 inhibitors in these patients, and the main mechanisms of cardiorenal protection.