Persistent wheezing, poorly responsive to bronchodilator therapy, raises concerns about the progression of cystic fibrosis-related lung disease. We describe 3 infants with such symptoms who were observed to have primary tracheomalacia. The diagnoses were made using flexible bronchoscopy during spontaneous respiration. Early recognition of this etiology can limit unnecessary investigation and the overuse of empirical treatments such as oral and inhaled corticosteroids.