The elastic pericardium exerts a compressive contact force on the surface of the myocardium that becomes more substantial when heart volume increases, as in patients with various forms of heart failure (HF). Pericardial restraint plays an important role in determining hemodynamics and ventricular function in both health and disease. This review discusses the physiology of pericardial restraint in HF and explores the question of whether it can be targeted indirectly through medical interventions or directly through a number of existing and future therapies.