Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of drugs which offer cardiovascular (CV) and renal benefits. They are currently indicated as first-line treatments of type 2 diabetes mellitus (T2DM) in patients with CV disease, high CV risk, renal disease, or heart failure with reduced ejection fraction (HFrEF). Two randomized clinical trials have shown the benefits of dapagliflozin and empagliflozin in patients with HFrEF, regardless of the presence of T2DM. Despite an overall favorable safety profile, attention has to be paid to adverse events, such as an increased risk of euglycemic diabetic ketoacidosis and genital mycotic infections. We present an up-to-date narrative literature review of the physiological mechanisms of action, current indications, and side effects of SGLT2 inhibitors.