Fatigue is one of the most burdensome symptoms in interstitial lung disease (ILD) and can have a major impact on quality of life, social interactions, and work capacity. The cause of fatigue is complex; it is caused or aggravated by a combination of different predisposing, precipitating, and perpetuating factors. There is no uniform definition of fatigue, but it is often divided in physical and mental components. Several validated questionnaires can be used for structural assessment of fatigue in daily care. Although the high burden of fatigue in ILD is recognized increasingly, studies that have investigated pharmacologic and nonpharmacologic treatment options are scarce. Because fatigue in ILD is often a multifactorial problem, therapeutic interventions ideally should be aimed at different domains. One of the first steps is to optimize treatment of the underlying disease. Subsequently, treatable causes of fatigue should be identified and treated. Recently, an increasing number of studies showed that supportive measures have the potential to improve fatigue. However, evidence-based treatment guidelines are lacking, and more research is highly needed in this field. In clinical practice, a comprehensive, multidisciplinary, and individually tailored approach seems best fit to optimize treatment of fatigue in patients with ILD.