Abstract The cardiovascular and renal systems are closely interconnected in health and disease. Disorders affecting one of these systems frequently involve the other. Both diseases progress through a continuous chain of events, defined as the ‘cardiorenal continuum’, which is initiated by risk factors that lead to subclinical disease, clinical events, and ultimately to heart failure and end-stage kidney disease. Previous studies have shown that interventions anywhere along this chain of events can interrupt the pathophysiological cascade and provide cardiovascular and/or kidney ‘protection’. More recently, clinical trials with SGLT-2 inhibitors (SGLT2i) have shown a significant reduction in cardiovascular and kidney outcomes. Evidence from EMPA-REG OUTCOME, CANVAS Program, DECLARE-TIMI 58, VERTIS-CV, CREDENCE, and more recently DAPA-HF, EMPEROR-Reduced, and DAPA-CKD show that the beneficial effects of SGLT2i are observed across all stages of the cardiorenal continuum, ranging from patients with diabetes and multiple risk factors to those with established cardiovascular disease and even independently of diabetes status. This review provides a critical appraisal of the efficacy and safety of SGLT2i, demonstrating that this is a novel way to disrupt the chain of pathological events in the cardiorenal continuum and prevent cardiovascular and kidney disease in patients with and without diabetes.