The renin-angiotensin system (RAS) plays an important role in regulating body fluids and blood pressure. However, inappropriate activation of the RAS contributes to the pathogenesis of cardiovascular and renal diseases. Recently, sodium glucose cotransporter 2 (SGLT2) inhibitors have been used as anti-diabetic agents. SGLT2 inhibitors induce glycosuria and improve hyperglycemia by inhibiting urinary reabsorption of glucose. However, in the early stages of treatment, these inhibitors frequently cause polyuria and natriuresis, which potentially activate the RAS. Nevertheless, the effects of SGLT2 inhibitors on RAS activity are not straightforward. Available data indicate that treatment with SGLT2 inhibitors transiently activates the systemic RAS in type 2 diabetic patients, but not the intrarenal RAS. In this review article, we summarize current evidence of the diuretic effects of SGLT2 inhibitors and their influence on RAS activity.