Abstract Heart failure with preserved ejection fraction (HFpEF) is a complex clinical condition. Initially called diastolic heart failure, it soon became clear that this condition is more than the opposite side of systolic heart failure. It is increasingly prevalent and lethal. Currently, HFpEF represents more than 50% of heart failure cases and shares a 90-day mortality and readmission rate similar to heart failure with reduced ejection fraction. Heart failure with preserved ejection fraction is best considered to be a systemic disease. From a cardiovascular standpoint, it is not just a stiff ventricle. A stiff ventricle combined with a stiff arterial and venous system account for the clinical manifestations of flash pulmonary edema and the marked changes in renal function or systemic blood pressure with minor changes in fluid volume status. No effective pharmacologic treatments are available for patients with HFpEF, but an approach to the musculoskeletal system has merit: the functional limitations and exercise intolerance that patients experience are largely due to abnormalities of peripheral vascular function and skeletal muscle dysfunction. Regular exercise training has strong objective evidence to support its use to improve quality of life and functional capacity for patients with HFpEF. This clinical review summarizes the current evidence on the pathophysiologic aspects, diagnosis, and management of HFpEF.