The natural history of chronic obstructive pulmonary disease (COPD) has classically been considered in terms of the rapid decrease in forced expiratory volume in 1 second (FEV(1)) and no other measure apart from smoking cessation has been demonstrated to modify the speed of this decrease. The evidence available from studies performed with tiotropium, of up to 1 year's duration, have shown that this anticholinergic drug can modify the course of COPD by acting on lung function, air entrapment, exacerbations, dyspnea and exercise tolerance, thus improving health status. This evidence has served as the basis for the design of the UPLIFT study (Understanding Potential Long-term Impacts on Function with Tiotropium), the main aim of which is to determine the effect of tiotropium on disease progression. This multicenter and multinational study has lasted for 4 years and almost 6,000 patients with COPD have participated. Data from this study are currently being analyzed and the results will shortly be made known. If the results are positive, it will be the first time that a pharmacological intervention has been able to modify the rate of FEV(1) decline, which would imply that the underlying disease is truly being modified. Positive data from the UPLIFT study would indicate that, together with smoking cessation, early treatment with tiotropium should be initiated at any stage of COPD, since both measures would have been proven to be able to modify the natural course of the disease. The probability of demonstrating maintenance of bronchodilation, as well as maintenance of the decrease in the number and severity of exacerbations found in studies conducted over a 1-year period, would represent a real change in what has been known to date about the natural course of COPD.