Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by decreased exercise capacity and fluid retention in the setting of preserved left ventricular systolic function and evidence of abnormal diastolic function. Therapeutic strategies include pharmacologic agents, pacing, baroreflex modification, diet, and exercise. Despite symptomatic and hemodynamic improvements with some therapies, large clinical trials have not demonstrated a clear improvement in clinical outcomes. The current management of patients with HFpEF is directed to symptomatic relief of congestion with diuretics and risk factor modification. In this article, we summarize the available evidence base for potential targets of therapy.