Cardiomyopathy is a major source of morbidity and mortality in Duchenne muscular dystrophy (DMD) patients now that respiratory care has improved. There is currently no definitive evidence guiding the management of DMD-associated cardiomyopathy (DMD-CM). The objective of this systematic review was to evaluate the effectiveness of pharmacotherapies for the prevention and/or management of DMD-CM and to determine the optimal timing to commence these interventions. A systematic search was conducted in January 2016 using MEDLINE, EMBASE and CINAHL databases and grey literature sources for studies evaluating the use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, beta-blockers or aldosterone antagonists. Study quality assessment was conducted using the Downs and Black quality assessment checklist. PRISMA reporting guidelines were used. Of the 15 studies included in this review, most were of low methodological quality. Meta-analysis was not possible due to heterogeneity of studies. ACE inhibitors, angiotensin receptor blockers, beta-blockers and/or aldosterone antagonists tended to improve or preserve left ventricular systolic function and delay the progression of DMD-CM. While there is evidence supporting the use of heart failure medication in patients with DMD, data regarding these interventions for delaying the onset of DMD-CM and when to initiate therapy are lacking. PROSPERO registration: CRD42015029555.