Definition of pulmonary rehabilitation The American Thoracic Society and the European Respiratory Society have recently adopted the following definition: pulmonary rehabilitation (PR) is an evidence-based, multidisciplinary, and comprehensive intervention for patients with chronic respiratory diseases who are symptomatic and often have decreased daily life activities. Integrated into the individualized treatment of the patient, PR is designed to reduce symptoms, optimize functional status, increase participation, and reduce healthcare costs through stabilizing or reversing systemic manifestations of the disease. Comprehensive PR programs include patient assessment, exercise training, education, and psychosocial support [Nici et al. 2006]. We will first address the pathophysiology and main consequences of chronic obstructive pulmonary disease (COPD), since it is a disease not only characterized by pulmonary inflammation and structural abnormalities leading to airflow obstructions, exercise limitation and symptoms of dispnea and fatigue, but also extended to a variety of systemic alterations. These extrapulmonary effects include systemic inflammation, nutritional abnormalities and weight loss, skeletal muscle dysfunction, and additional organ effects. The high burden of COPD is further contributed to by systemic effects, leading to a pronounced deterioration in health status and a diminished quality of life (QoL). Chronic obstructive pulmonary disease: pathophysiology and consequences Peripheral and respiratory muscles dysfunction The principal symptom limiting exercise in patients with COPD is dyspnea, due to changes in the respiratory mechanics and impaired pulmonary gas exchange (Table 1). Hamilton and colleagues [Hamilton et al. 1996] noted that lower limb fatigue in isolation was greater than the sensation of dyspnea in 43% of patients with COPD who had maximal exercise testing. Although lower limb muscles are largely responsible for limiting activities such as walking and going up inclines or