Heart failure (HF) is a major public health problem with an increasing prevalence among aging populations and individuals with type 2 diabetes. The pathophysiology of HF is complex and results from various detrimental pathways (inflammation, oxidative stress, endothelial dysfunction, adverse remodeling, and decreased autophagic flux, among others) that contribute to a failure of cardiac output. While the introduction of sodium-glucose cotransporter 2 inhibitors (SGLT2is), originally designed as antidiabetic medications for the treatment of T2D, has revolutionized the treatment of HF and are currently formally recommended for its treatment, according to relevance to the societal guidelines. No other oral antidiabetic medications except SGLT2is to date have shown the significant benefit on HF events. However, despite SGLT2is’ possible wide clinical implications, there are lots of questions to unravel the mechanisms underlying their mode of action. This article provides an overview of the major cardiovascular outcome trials assessing the effectiveness of SGLT2is in the management of HF and of the diverse mechanisms of action through which SGLT2is exert their benefits in this setting. These mechanisms will be mainly focused on the “off-target” direct cardiac effects of SGLT2i, which may help explain the beneficial effects of SGLT2is on patients with HF, irrespective of their diabetes status. Nevertheless, given notably absence of SGLT2 in the cardiac myocardium, the evidence suggests that SGLT2independent effects of this drug class likely occurs through off-target effects in the myocardium. Thus, further research is required to investigate the potential mechanisms underlying the effect of SGLT2is on cardiac cells and to provide mechanistic and additional clinical evidence regarding the various effects of SGLT2is across the spectrum of HF.