Cancer-related fatigue (CRF) is a highly prevalent and the most distressing symptom during and after treatment for cancer. It is characterized by feelings of physical and mental tiredness, weakness, and lack of energy and is not influenced by rest or sleep. Approximately 40% of patients suffer from CRF at diagnosis and nearly all patients experience fatigue during the course of cancer therapy. The impact of CRF on daily living and patient quality of life (QoL) is substantial. It profoundly affects patient quality of life and limits personal, social and occupational roles. The fatigue is also associated with significant levels of distress and it imposes a financial burden by limiting the ability to work. The underlying causes of CRF are poorly understood as are the relationship between fatigue and psychosocial distress, depression or anxiety. This paper seeks to give an overview of cancer-related fatigue and its psychosocial burden.