Summary: Sodium-glucose cotransporter 2 inhibitors (SGLT2) are a new class of drugs originally used in the treatment of type 2 diabetes mellitus (T2DM). Their pleiotropic mechanism of action includes a nephroprotective effect that is primarily independent of glucose regulation. The beneficial influence of SGLT2 inhibitors on renal function include both systemic processes and regulation of renal hemodynamics. Potential mechanisms include reduction of glomerular hyperfiltration, stimulation of osmotic diuresis and natriuresis, metabolic changes, or reduction of renal hypoxia. This unique mechanism of action has led SGLT2 to attract the interest of clinicians as potential treatment for conditions other than T2DM, particularly chronic kidney disease (CKD) and heart failure (HF). Clinical trials have shown that SGLT2 inhibitors reduce the risk of renal death, end-stage renal disease (ESRD), or the need to initiate kidney replacement therapy in patients with CKD and increased cardiovascular risk. Thus, SGLT2 inhibitors may be beneficial in the treatment of patients with HF who often have coexisting renal dysfunction. The aim of this study is to summarize recent clinical trial results and analyze potential mechanisms underlying the nephroprotective effect of SGLT2 inhibitors in a population of patients with impaired renal function and increased cardiovascular risk.