Background: Improved respiratory care of Duchenne muscular dystrophy (DMD) patients has unmasked cardiomyopathy as a major source of morbidity and mortality. There is currently no consensus regarding the management of DMD-associated cardiomyopathy (DMD-CM). The objective of this systematic review was to evaluate the efficacy of pharmacological therapies for prevention and management of DMD-CM, and determine the optimal timing to commence these interventions. Methods: A systematic search was conducted in October 2015 and updated in January 2016 using MEDLINE, EMBASE and CINAHL databases and 9 grey literature sources for studies evaluating the use of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), beta-blockers (BB) or aldosterone antagonists (AA) in DMD patients. References of retrieved records were searched. Quality assessment was conducted using the Downs and Black Quality Assessment Checklist. PRISMA reporting guidelines were used. Results: The 11 included studies were of low methodological quality. However, the use of an ACEi, ARB, BB and AA tended to improve or preserve left ventricular systolic function and delay the progression of cardiomyopathy. Conclusions: While there is evidence supporting the use of heart failure medication in patients with DMD-CM, data regarding these interventions for delaying the onset of DMD-CM and when to initiate therapy is lacking.