Duchenne muscular dystrophy mouse models have a predictable and reproducible time course of cardiomyopathy progression with discrete pathogenic steps, which closely parallel what we know occurs in the cardiomyopathy of patients with Duchenne muscular dystrophy. The slow progression of early pathogenic steps common to many cardiomyopathies may make Duchenne muscular dystrophy models useful for identifying novel treatment targets and testing the therapeutic value of new treatment paradigms for an at-risk patient population far beyond those with muscular dystrophies. Dilated cardiomyopathy is a leading cause of death in individuals affected by Duchenne muscular dystrophy (DMD), and nearly all DMD patients develop dilated cardiomyopathy by age 18. DMD and the milder Becker muscular dystrophy result from mutations in the X-linked gene encoding dystrophin, a membrane-associated protein that helps protect striated muscle cell membranes from damage. Clinical signs resulting from lower limb muscle weakness lead to DMD diagnosis typically by 5 years of age and loss of ambulation by 12 years of age. Skeletal myopathy in Becker muscular dystrophy has a later age of onset and slower progression than DMD, and dilated cardiomyopathy is the primary cause of mortality. Earlier ventilatory support for affected respiratory muscles and timely management of pulmonary infections have led to increased survival for DMD patients into their mid-twenties. These advances have made increasingly evident the underlying cardiomyopathy that presents as heart failure and often fatal arrhythmias in the later decades of life. Despite the devastating consequences of DMD cardiomyopathy, its unique features may provide new insights into myocardial disease. First, the consistent lag between evident skeletal myopathy and cardiomyopathy affords early detection and possible treatment of a patient population that is genetically programmed to develop cardiac dysfunction. Second, the myocardial disease exhibits a relatively slow progression, providing the ability to understand each step involved. Third, there are isogenic …