In chronic lung diseases physical activity limitation is multifactorial involving respiratory, hemodynamic, and peripheral muscle abnormalities. The mechanisms of limitation discussed in this paper relate to (i) the imbalance between ventilatory capacity and demand, (ii) the imbalance between energy demand and supply to working respiratory and peripheral muscles, and (iii) the factors that induce peripheral muscle dysfunction. In practice, intolerable exertional symptoms (i.e., dyspnea) and/or leg discomfort are the main symptoms that limit physical performance in patients with chronic lung diseases. Furthermore, the reduced capacity for physical work and the adoption of a sedentary lifestyle, in an attempt to avoid breathlessness upon physical exertion, cause profound muscle deconditioning which in turn leads to disability and loss of functional independence. Accordingly, physical inactivity is an important component of worsening the patients’ quality of life and contributes importantly to poor prognosis. Identifying the factors which prevent a patient with lung disease to easily carry out activities of daily living provides a unique as well as important perspective for the choice of the appropriate therapeutic strategy.