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Funding Information: José Silva-Cardoso has received speaker and consultant fees, advisory board participation fees, or investigational grants from Abbott, AstraZeneca Pharmaceuticals, Bial, Boehringer Ingelheim, Menarini, Merck Serono, Merck Sharp & Dohme, Novartis, Orion, Pfizer, Sanofi, Servier, and Vifor Pharma. Aurora Andrade has received speaker or advisory boards fees from Novartis, AstraZeneca, Servier, Orion and Bial. Dulce Brito has received speaker and consultant fees or investigational grants from AstraZeneca Pharmaceuticals, Boehringer Ingelheim, Novartis, Orion, Pfizer, Roche Diagnostics, Sanofi, Servier, and Vifor Pharma. Jorge Ferreira has received speaker and consultant fees from Amgen, AstraZeneca, Boehringer-Ingelheim, Novartis. Cândida Fonseca has received speaker and consultant fees, or investigational grants, from AstraZeneca Pharmaceuticals, Bayer, Boehringer Ingelheim, Merck Serono, Novartis, Orion, Pfizer, Sanofi, Servier, and Vifor Pharma. Marisa Peres has received speaker or advisory board fees from AstraZeneca, Servier, and Novartis. Fátima Franco has received speaker or advisory board fees from Boehringer, AstraZeneca, Novartis and Servier. Brenda Moura has received speaker or advisory board fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Servier, Novartis, Vifor Pharma. Publisher Copyright: © 2021 Sociedade Portuguesa de Cardiologia Copyright: Copyright 2021 Elsevier B.V., All rights reserved. Heart failure (HF) is a major health problem with a significant impact on morbidity, mortality, quality of life and healthcare costs. Despite the positive impact of disease-modifying therapies developed over the last four decades, HF mortality and hospitalization remain high. We aim at reviewing the evidence supporting the use of sodium-glucose co-transporter-2 (SGLT-2) inhibitors, as a novel strategy for HF with reduced ejection fraction (HFrEF) treatment. The consistent observation of a reduction in HF hospitalizations in type-2 diabetes cardiovascular safety trials EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58 and VERTIS raised the hypothesis that SGLT-2 inhibitors could have an impact in HF treatment. This hypothesis was first confirmed in 2019 with the DAPA-HF publication showing that dapagliflozin on top of optimized HFrEF therapy, reduced HF-hospitalizations and cardiovascular mortality. This was reinforced by the EMPEROR-Reduced publication in 2020 showing that empagliflozin on top of optimized HFrEF therapy, reduced HF-hospitalizations. Both studies established SGLT-2 inhibitors as a fourth pillar of HFrEF prognosis-modifying therapy, in addition to the gold standard triple neurohormonal modulation/blockade. publishersversion published