Peripheral skeletal muscle dysfunction is considered to be one of the primary determinants of disability in chronic obstructive pulmonary disease (COPD; 1). Furthermore, the poor relationship between exercise capacity and lung function impairment in COPD suggests exercise intolerance in this patient group is not limited by pulmonary ventilation. This stand-point is supported by the observations that improvements in dyspnoea and exercise capacity that result from lung directed therapies are small relative to those seen following exercise training mediated pulmonary rehabilitation. Unlike normal healthy ageing where the loss of Type II muscle fibres predominates, COPD is characterised by the preferential loss of type I muscle fibres and a reduction in the maximal activity of several mitochondrial enzymes. It is unclear whether these responses are attributable to inactivity induced deconditioning rather than COPD per se. As might be expected, there is a reduction in mitochondrial ATP generation and greater reliance on non-mitochondrial energy production during exercise in COPD patients. Skeletal muscle adenine nucleotide loss is associated with fatigue during high intensity exercise in healthy volunteers, and reflects the inability of muscle ATP production to match the ATP demand of contraction. We have demonstrated that significant adenine nucleotide loss occurs in the skeletal muscles of COPD patients during exercise at considerably lower absolute workloads to those seen in healthy volunteers (2). Furthermore, efforts to reduce the magnitude of metabolic stress at the onset of exercise by pharmacologically activating the pyruvate dehydrogenase complex immediately prior to exercise, using a pyruvate dehydrogenase kinase inhibitor, reduced blood lactate and ammonia (a sensitive marker of adenine nucleotide loss) accumulation during exercise and improved maximal exercise performance in COPD patients (3). It is perhaps not surprising therefore that endurance exercise rehabilitation is effective at improving exercise capacity in COPD. COPD patients have a lower muscle mass and strength compared to age and sex matched controls, and both are predictors of mortality, disability and healthcare utilisation in COPD, independent of lung function impairment (4, 5). Nonetheless, the aetiology of this phenotype is unknown. Several studies have shown functional benefits from resistance training in COPD. However, whilst resistance exercise training promotes muscle mass restoration after disuse in young (6) and older (7) people (albeit to a lesser extent in the latter), the impact of resistance training on muscle mass restoration in COPD, and the mechanisms therein, is less clear cut. This is at least partly attributable to progress in COPD being hampered by a lack of exercise intervention studies documenting temporal changes in genes and proteins thought to regulate muscle mass, and the dovetailing these observations with sensitive measures of muscle mass and muscle protein synthesis and breakdown. These are important generic issues because the choice of likely therapeutic approaches in COPD will depend upon the outcome of such studies.