Chronic obstructive pulmonary disease (COPD) is characterised by a range of pathological changes of the respiratory system, including airflow limitation secondary to structural changes of the small airways and loss of alveolar attachments, inflammation, ciliary dysfunction, and increased mucous production. COPD also has significant systemic consequences. The relationships between these pulmonary and nonpulmonary morbidities are not fully understood, and this further complicates the assessment of disease severity and prognosis. Although improving lung function and disease symptoms have been the main focus of COPD management, these parameters alone do not reflect the full burden of disease. More recent endeavours have highlighted the potential role of addressing physical limitations imposed by systemic alterations. It is evident that systemic manifestations are common in COPD. Indeed, many patients demonstrate a gradual and significant weight loss that exacerbates the course and prognosis of disease. This weight loss is often accompanied by peripheral muscle dysfunction and weakness, which markedly contribute to exercise limitation and impaired quality of life. Weight loss has been postulated to be the result of a high metabolic rate that is not compensated for by increased dietary intake. The cause of this elevated metabolism is a matter of much debate, and several factors have been implicated. Similarly, the processes underlying depletion of muscle mass and function have not been fully delineated. The impact of the systemic manifestations of COPD is substantial, and although many attempts have been made to elucidate the mechanisms underlying these manifestations, there are important questions, which remain to be answered. An increase in our understanding in this field will doubtless highlight potential therapeutic targets, and assist in guiding future therapeutic development.