Heart failure is a global epidemic with limited therapy. Abnormal left ventricular wall stress in the diseased myocardium results in a biochemical positive feedback loop that results in global ventricular remodeling and further deterioration of myocardial function. Mechanical myocardial restraints such as the Acorn CorCap and Paracor HeartNet ventricular restraints have attempted to minimize diastolic ventricular wall stress and limit adverse ventricular remodeling. Unfortunately, these therapies have not yielded viable clinical therapies for heart failure. Cellular and novel biopolymer-based therapies aimed at stabilizing pathologic myocardium hold promise for translation to clinical therapy in the future.