Sodium–glucose cotransporter-2 (SGLT2) inhibitors recently emerged as an effective therapy for heart failure (HF) with reduced ejection fraction. Recent published clinical trials have confirmed these agents substantially reduce mortality and HF hospitalization among patients with established HF with reduced ejection fraction, with or without type 2 diabetes. Ongoing studies are evaluating the effects of SGLT2 inhibitors on clinical outcomes for patients with HF with preserved ejection fraction. Nurse practitioners must understand the indications and mechanisms of SGLT2 inhibitors when prescribing. Thoughtful collaboration between cardiology and endocrine providers can guide management with the use of SGLT2 inhibitors in complicated HF patients.