Heart failure (HF) accounts for nearly 1 million hospitalizations and more than 300 000 deaths annually. Emerging data support the benefit of a novel class of therapies, sodium-glucose cotransporter-2 inhibitors (SGLT2i), for treatment of HF with reduced ejection fraction and prevention of HF in individuals with diabetes or chronic kidney disease (CKD). However, SGLT2i have not yet been shown to lower HF risk in a broader population at risk for HF without diabetes or CKD. The narrative around flozins may sound familiar: it has striking parallels to the 1990s when the emergence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, shifted the focus from secondary prevention of atherosclerotic cardiovascular disease (ASCVD) to primary prevention in those at risk. In this Viewpoint, we synthesize available data for the role of SGLT2i in HF and propose a theoretical framework to evaluate flozins in primary prevention of HF akin to the role of statins in ASCVD (Figure).