Skeletal muscle dysfunction occurs in patients with chronic obstructive pulmonary disease (COPD) and affects both ventilatory and nonventilatory muscle groups. It represents a very important comorbidity that is associated with poor quality of life and reduced survival. It results from a complex combination of functional, metabolic, and anatomical alterations leading to suboptimal muscle work. Muscle atrophy, altered fiber type and metabolism, and chest wall remodeling, in the case of the respiratory muscles, are relevant etiological contributors to this process. Muscle dysfunction worsens during COPD exacerbations, rendering patients progressively less able to perform activities of daily living, and it is also associated with poor outcomes. Muscle recovery measures consisting of a combination of pulmonary rehabilitation, optimized nutrition, and other strategies are associated with better prognosis when administered in stable patients as well as after exacerbations. A deeper understanding of this process’ pathophysiology and clinical relevance will facilitate the use of measures to alleviate its effects and potentially improve patients’ outcomes. In this review, a general overview of skeletal muscle dysfunction in COPD is offered to highlight its relevance and magnitude to expert practitioners and scientists as well as to the average clinician dealing with patients with chronic respiratory diseases.