Duchenne muscular dystrophy (DMD) is the most common hereditary neuromuscular disease in children. It is an X-linked hereditary dystrophinopathy due to the absence of dystrophin. Its onset is often in early childhood and presents with proximal distribution of weakness and a progressive course. Cardiac involvement in DMD is common, and its onset is usually after the age of 10 years. The most common cardiac manifestations are a dilated cardiomyopathy and cardiac arrhythmia. However, pericardial effusion with cardiac tamponade is a very rare cardiac complication of DMD. We report a boy with DMD who initially presented with progressive dyspnea and an enlarged cardiac silhouette on chest radiography who subsequently developed a large pericardial effusion with cardiac tamponade. Early recognition of pericardial effusion with cardiac tamponade is important for institution appropriate therapy.