Airway inflammation and remodeling in asthma occur in the central airways and also in the small airways and in the lung parenchyma. The small airways and the lung parenchyma can produce many Th2 cytokines, chemokines, and mediators involved in initiation and perpetuation of the inflammatory process. The distal lung has been recognized as a predominant site of airflow obstruction in asthmatics. Distal inflammation has been described as more severe than large airway inflammation, and strong evidence of remodeling in the lung periphery is emerging. Recognition of asthma as a disease of the entire respiratory tract has clinical significance, highlighting the need to target the distal lung in any strategy for effective treatment of this disease.