Irreversible airflow obstruction or limitation occurs in some patients with asthma, can develop early in life, and becomes more common as asthma becomes more severe. Efforts to understand irreversible airflow obstruction or limitation have been hampered by the lack of a standardized definition of the phenotype and by the lack of appropriate research models. Unfortunately, it appears that currently available asthma treatments do not prevent this important asthma complication. Herein, the evidence of an irreversible component of asthma, its underlying pathology, and the limitations of current asthma treatments are reviewed.