We summarize what is known about the clinical epidemiology, pathophysiology, and prognosis for patients with HFmrEF and how these features compare with the more well-studied HF groups. Although recommended treatments currently focus on aggressive management of comorbidities, we summarize the studies that identify a potential signal for beneficial therapies. Future studies are needed to not only better characterize the HF population but also determine effective management strategies to reduce the high cardiovascular morbidity and mortality burden on this phenotype of patients with HF.