Heart failure with preserved ejection fraction (HFpEF) remains a diagnostic and treatment challenge with its different phenotypic presentation despite its growing prevalence with associated increase in morbidity and mortality. Traditional approaches of heart failure (HF) management based on the neurohormonal hypothesis targeting the renin-angiotensin-aldosterone (RAAS) inhibition have been highly successful in the treatment of heart failure with reduced ejection fraction (HFrEF) but failed to produce outcome benefits in HFpEF. Recent experimental data and the robust outcome benefits from Sodium-Glucose Co-Transporter 2 inhibitor (SGLT2i) trials shed further light into the cellular hypothesis of HF, probablymore so for HFpEF. Contrary to the generalized approach, recent focus of research has shifted to phenotype specific mechanisms, targeting of which are expected to result in better outcomes in the management of HFpEF. Apart from life style modification and the currently available limited therapy with SGLT2i, more cellular level interventions and perhapsgene-specific therapy may hold promise in the future direction of HFpEF treatment.