Heart failure with preserved ejection fraction (HFpEF) affects half of all heart failure (HF) patients. Despite similar morbidity and mortality rates to HF with reduced ejection fraction (HFrEF), no effective treatment has been identified. HFpEF is characterized by diastolic dysfunction, but recent studies show that multiple non-diastolic abnormalities also contribute. Diagnosis is challenging and relies on clinical evaluation, echocardiography, and invasive hemodynamic assessment. The review discusses the pathophysiology, diagnosis, and treatment of HFpEF, highlighting novel therapeutic strategies under investigation. HFpEF is often referred to as 'diastolic' HF (DHF), but this term is now replaced by HFpEF or HF with normal left ventricular ejection fraction (HFnEF). The term HFpEF has limitations, as it implies a pre-existing ejection fraction, which is not always known. HFpEF is currently observed in 50% of HF patients, with outcomes similar to HFrEF. However, the prognosis is poor due to complex multisystem involvement, including skeletal muscle and vascular dysfunction, pulmonary hypertension, renal failure, anemia, and atrial fibrillation. The prevalence of HFpEF is rising rapidly, making it the most common HF phenotype in the next decade, but no improvements in outcomes have been realized over the past two decades. The pathophysiology of HFpEF involves diastolic dysfunction, characterized by prolonged isovolumic relaxation, slow LV filling, and increased diastolic stiffness. Recent studies have identified additional mechanisms, including systolic dysfunction, impaired ventricular-vascular coupling, abnormal vasodilation, chronotropic incompetence, and pulmonary hypertension. The extracellular matrix and cardiomyocytes contribute to diastolic dysfunction, with collagen deposition and cardiomyocyte stiffness playing key roles. Matricellular proteins also influence fibroblast function and cardiomyocyte hypertrophy. Systolic dysfunction in HFpEF is not as severe as in HFrEF, but recent studies show that even mild limitations in contractility can become problematic during exercise. Ventricular-arterial coupling and vascular dysfunction are also important in HFpEF, with increased stiffness leading to greater blood pressure variability. Vascular dysfunction in HFpEF may be due to endothelial dysfunction, and therapies targeting combined ventricular-arterial stiffening improve exercise capacity in elderly hypertensive patients. Diagnosis of HFpEF requires signs and symptoms of HF, normal systolic LV function, and evidence of diastolic dysfunction. Guidelines for diagnosis include echocardiography, plasma natriuretic peptides, and invasive hemodynamic assessment. The E/E' ratio is a key marker of diastolic dysfunction, with E/E' >8 providing stand-alone evidence. However, the diagnostic value of E/E' is being evaluated in ongoing trials. Treatment of HFpEF remains challenging, with no proven effective therapies. Trials have shown that ACEHeart failure with preserved ejection fraction (HFpEF) affects half of all heart failure (HF) patients. Despite similar morbidity and mortality rates to HF with reduced ejection fraction (HFrEF), no effective treatment has been identified. HFpEF is characterized by diastolic dysfunction, but recent studies show that multiple non-diastolic abnormalities also contribute. Diagnosis is challenging and relies on clinical evaluation, echocardiography, and invasive hemodynamic assessment. The review discusses the pathophysiology, diagnosis, and treatment of HFpEF, highlighting novel therapeutic strategies under investigation. HFpEF is often referred to as 'diastolic' HF (DHF), but this term is now replaced by HFpEF or HF with normal left ventricular ejection fraction (HFnEF). The term HFpEF has limitations, as it implies a pre-existing ejection fraction, which is not always known. HFpEF is currently observed in 50% of HF patients, with outcomes similar to HFrEF. However, the prognosis is poor due to complex multisystem involvement, including skeletal muscle and vascular dysfunction, pulmonary hypertension, renal failure, anemia, and atrial fibrillation. The prevalence of HFpEF is rising rapidly, making it the most common HF phenotype in the next decade, but no improvements in outcomes have been realized over the past two decades. The pathophysiology of HFpEF involves diastolic dysfunction, characterized by prolonged isovolumic relaxation, slow LV filling, and increased diastolic stiffness. Recent studies have identified additional mechanisms, including systolic dysfunction, impaired ventricular-vascular coupling, abnormal vasodilation, chronotropic incompetence, and pulmonary hypertension. The extracellular matrix and cardiomyocytes contribute to diastolic dysfunction, with collagen deposition and cardiomyocyte stiffness playing key roles. Matricellular proteins also influence fibroblast function and cardiomyocyte hypertrophy. Systolic dysfunction in HFpEF is not as severe as in HFrEF, but recent studies show that even mild limitations in contractility can become problematic during exercise. Ventricular-arterial coupling and vascular dysfunction are also important in HFpEF, with increased stiffness leading to greater blood pressure variability. Vascular dysfunction in HFpEF may be due to endothelial dysfunction, and therapies targeting combined ventricular-arterial stiffening improve exercise capacity in elderly hypertensive patients. Diagnosis of HFpEF requires signs and symptoms of HF, normal systolic LV function, and evidence of diastolic dysfunction. Guidelines for diagnosis include echocardiography, plasma natriuretic peptides, and invasive hemodynamic assessment. The E/E' ratio is a key marker of diastolic dysfunction, with E/E' >8 providing stand-alone evidence. However, the diagnostic value of E/E' is being evaluated in ongoing trials. Treatment of HFpEF remains challenging, with no proven effective therapies. Trials have shown that ACE