Dyspnea, a symptom limiting exercise capacity in patients with COPD, is associated with central perception of an overall increase in central respiratory motor output directed preferentially to the rib cage muscles. On the other hand, disparity between respiratory motor output, mechanical and ventilatory response of the system is also thought to play an important role on the increased perception of exercise in these patients. Both inspiratory and expiratory muscles and operational lung volumes are important contributors to exercise dyspnea. However, the potential link between dyspnea, abnormal mechanics of breathing and impaired exercise performance via the circulation rather than a malfunctioning ventilatory pump per se should not be disregarded. Change in arterial blood gas content may affect dyspnea via direct or indirect effects. An increase in carbon dioxide arterial tension seems to be the most important stimulus overriding all other inputs from dyspnea in hypercapnic COPD patients. Hypoxia may act indirectly by increasing ventilation and indirectly independent of changes in ventilation. A greater treatment effect is often achieved after the addition of pulmonary rehabilitation with pharmacological treatment.