Introduction: Exercise limitation in chronic obstructive pulmonary disease (COPD) is multi-factorial; however, growing evidence indicates that muscle dysfunction may contribute in some patients. Areas covered: This work outlines current evidence for and against increased peripheral muscle fatigability in COPD through a comprehensive review of relevant literature available on PubMed/MEDLINE until May 2020. The authors first discuss key methodological issues relative to muscle fatigue assessment by non-volitional techniques, particularly magnetic stimulation. The authors then provide a detailed discussion of critical studies to have objectively measured skeletal muscle fatigue in individuals with COPD. Expert opinion: Current evidence indicates that localized (knee extension) and cycling exercise are associated with increased quadriceps fatigability in most COPD patients. Increased fatigability, however, has not been consistently found in response to walking, likely reflecting the tendency of 'central' respiratory constraints to overshadow potential functional impairments in the appendicular muscles in this form of exercise. Thus, addressing skeletal muscle abnormalities may be critical to translate improvements in lung mechanics (e.g., due to bronchodilator therapy) into better exercise tolerance. The positive effects of pulmonary rehabilitation on muscle fatigability are particularly encouraging and suggest a role for these measurements to test the efficacy of emerging adjunct training strategies focused on the peripheral muscles.