Structural changes in COPD are found in the central airways, peripheral airways, lung parenchyma, and pulmonary vasculature. Broadly there are two different pathways leading to the same physiologic phenotype: one centered on the small airways and involving mucosal inflammation and structural change, and the other centered on the parenchyma involving excessive proteolysis and /or disordered repair processes. A highly variable combination of these changes exists in different patients, in part due to genetic factors. The composite picture seen on pulmonary function tests is evidence of over-inflation of the lung, decreased airflow and abnormalities in gas exchange. Earlier stages of the airway disease are associated with more potentially reversible changes, whereas later stages show more collagen deposition and hence irreversibility. Thus a careful assessment of the structural phenotype of subpopulations of COPD patients is likely to lead to optimal categorization for therapeutic trials, and earlier disease is more likely to response to interventions.