Chronic obstructive pulmonary disease (COPD) is a progressive disease with studies of disease progression generally focusing on measures of airflow and mortality. In nonsmokers, maximal lung function is attained around age 15 to 25 years, and after a variable plateau phase, subsequently declines at approximately 20 to 25 ml/year. Smoking may reduce the maximal FEV(1) achieved, shorten or eliminate the plateau phase, and may accelerate the rate of decline in lung function in a dose-dependent manner. Some smokers are predisposed to more rapid declines in lung function than others, and recent reports suggest that females may be at higher risk of lung damage related to smoke exposure than males. Progressive deterioration in dyspnea, functional status, and health-related quality of life (HRQL) in patients with COPD is well known, but the magnitude and rate of decline and its association with severity of airflow obstruction remains poorly defined. Many studies have identified pulmonary function, in particular the FEV(1), as the single best predictor of survival. An impaired diffusing capacity and overall impairment in functional status have also been associated with impaired survival in COPD. The National Emphysema Treatment Trial has provided additional insight into these features in a large, well-characterized group of patients with severe airflow obstruction and structural emphysema.