Hyperinflation of the lungs is associated with activity limitation and reduced quality of life of patients with chronic obstructive pulmonary disease (COPD). Cardiopulmonary exercise testing has proven useful, not only in establishing this link, but also in determining which interventions modify exercise endurance and the mechanisms by which this is achieved. In COPD, dynamic hyperinflation is reduced during exercise by interventions that either increase the potential for expiratory flow or increase the time available for expiration. Two classes of intervention improve exercise tolerance by increasing expiratory flow. Bronchodilators reduce expiratory airflow resistance by increasing the diameter of the airways. An alternative intervention, though less practical, is to reduce the density of the gas exhaled through obstructed airways, such as occurs when breathing a mixture of helium and oxygen (heliox). In contrast, supplemental oxygen and exercise rehabilitation programs improve endurance by reducing respiratory ventilatory drive and, therefore, respiratory rate. The different mechanisms exploited by these interventions to reduce dynamic hyperinflation suggest that combination treatments should yield additive benefits. This has been proven in the case of combinations of rehabilitative exercise training with supplemental oxygen, or with the bronchodilator tiotropium, both of which have been found to yield additive effects. With such interventions, we already have options for improving the mobility of patients with COPD. With a firm understanding of the physiologic basis of exercise limitation, we can focus on defining new and better strategies to improve exercise tolerance.