: In individuals with type 2 diabetes mellitus, sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and serious adverse renal events, both in randomized controlled trials and observational studies. : In this paper, the authors critically discuss the rationale, results and implications of the recent placebo-controlled EMPEROR-Reduced trial [NCT03057977], which evaluated empagliflozin in subjects with chronic heart failure and a reduced ejection fraction (HFrEF), with or without diabetes. A parallel with the DAPA-HF trial, investigating dapagliflozin in a similar albeit not fully overlapping population, is also provided. The authors finally provide the reader with their expert perspectives. : EMPEROR-Reduced confirmed and extended the findings from DAPA-HF, especially on renal outcomes, thus strengthening the rationale for considering SGLT2 inhibitors among established treatments in HFrEF. Forthcoming guidelines supported by knowledge of the clinical pharmacology of SGLT2 inhibitors will hopefully assist cardiologists, nephrologists and general practitioners in selecting the target population and promoting safe prescribing.