Progressive abnormalities of passive stiffness or active relaxation of the myocardium that impair ventricular filling during diastole may be an important contributor to the development of heart failure in patients with preserved ejection fraction. In this review, we discuss the epidemiology and pathophysiology of diastolic dysfunction and heart failure with preserved ejection fraction, highlighting potential therapeutic approaches and exploring the limited available evidence base for improving clinical outcomes in patients with these challenging entities.