A 4-month-old infant with trisomy 21 is brought to the emergency department for breathing difficulty. Subsequently, he is diagnosed with a Morgagni diaphragmatic hernia. Tachypnea in an infant with trisomy 21 may be the result of diagnosis such as congenital heart disease, infectious processes, structural anomalies, or aspiration secondary to gastroesophageal reflux or swallowing dysfunction. Knowledge of these abnormalities is important when generating a differential diagnosis in these patients. Although uncommon, a Morgagni hernia may present beyond the newborn period and should be considered when evaluating an infant with trisomy 21 and respiratory difficulty.