Muscle function is essential for both ventilation (respiratory muscles) and interacting with the environment (peripheral muscles). One of the systemic manifestations of chronic obstructive pulmonary disease COPD is skeletal muscle dysfunction. While the causes of this dysfunction are poorly understood, various local and systemic factors appear to play a role. Among the systemic factors are those arising from the lung disease itself, which increases respiratory muscle activity, leads to unfavorable geometric relationships, and results in a reduction in the patients use of the peripheral musculature. Other systemic factors include inflammation and oxidative stress, malnutrition, impaired gas exchange, comorbidity, and certain myotoxic drugs. Local factors include muscle inflammation and oxidative stress, apoptosis, injury, and impaired regenerative capacity. All of these factors interact in different ways in each muscle group, giving rise to various phenotypes and specific contractile capacities.