The aim of this supplement is to discuss the important role of the kidney in glucose homeostasis. It produces glucose via gluconeogenesis, it filters glucose from the blood, and reabsorbs the filtered glucose in the proximal tubule, mainly via the sodium-glucose cotransporter-2 (SGLT-2). SGLT-2 is paradoxically upregulated in individuals with type 2 diabetes (T2D), which results in increased glucose reabsorption and hyperglycemia. This core defect in the pathophysiology of T2D provides the rationale for the use of SGLT-2 inhibitors to increase urinary glucose excretion and reduce hyperglycemia in an insulin-independent manner. Benefits of SGLT-2 inhibitor use in patients with T2D, in addition to improved glycemic control, include modest weight loss, decreased systolic blood pressure, reduced serum uric acid, and reduced risk of cardiovascular events. Common adverse events are urinary tract infection and genital mycotic infections. The risk of hypoglycemia is low with SGLT-2 inhibitors, particularly when they are given as monotherapy.