Fatigue is a symptom commonly diagnosed in cancers and in many other chronic debilitating diseases and is one of the main therapeutic targets for various pharmacologic and non-pharmacologic interventions. However, in chronic obstructive pulmonary disease (COPD), this symptom, which can be considered as the main extrapulmonary clinical feature of the disease, can impact significantly on the health-related quality of life of the patients. The aims of this review are to discuss the issues related to fatigue assessment in COPD and to highlight the importance of this symptom in this setting based on the data retrieved from articles published between 1987 through August 2014 available on MEDLINE database. Fatigue can be measured by various scales or questionnaires that are designed for generic purposes or for COPD-related purposes but is still underdiagnosed and undertreated. This is due to the fact that its clinical and prognostic relevance are not appropriately acknowledged. The early identification of fatigue clinical descriptors from patients’ reports could help with better management of this symptom.