Abnormal physical exhaustion and fatigue are often simply regarded as a natural consequence of pulmonary diseases. Apart from factors not specifically related to pulmonary diseases (e.g. consequences of infections or malignant diseases of the lungs), increased work of breathing due to impaired lung/thoracic cage mechanics, the effects of chronic hypoxia and hypercapnia, the consequences of disturbed sleep and psychosocial factors are mainly responsible for the impaired physical fitness and the fatigue in association with lung diseases. A careful case history including psychosocial aspects and a thorough physical examination are essential for an efficient diagnostic evaluation. Tests of pulmonary function not only in the awake patient at rest, but also during sleep or adequate physical exercise can reveal the causes of impaired physical performance and fatigue related to lung diseases.