Large airway diseases manifest in ways distinct from those of small airway diseases. Noisy breathing that begins early in life suggests a congenital lesion of the large airways. The findings of elevated respiratory rate, in conjunction with subcostal retractions, hyperinflation to percussion, and musical wheezes, are diagnostic of small airway obstruction. Differentiating large from small airway disease is crucial, because each disease has a distinct diagnosis, and treatment of the 2 disease types can be quite different. When these principles are applied to a patient with wheezing or other signs of airway compromise, it becomes fairly easy to differentiate large from small airway disease. The treatment of patients with large airway disease can be substantially different from that of patients with small airway disease. Being able to differentiate the two is critically important. With the use of the history, physical examination, and radiographic evaluations described earlier, nearly every patient can be given an accurate diagnosis and treated appropriately.