Cancer-related fatigue (CRF) is one of the most common symptoms reported by patients and is defined as the feeling of extraordinary exhaustion associated with a high level of distress, disproportionate to the patients' activity, and is not relieved by sleep or rest. Prevalence rates range from 59 to nearly 100% depending on the clinical status of the cancer. Except for chemotherapy-induced anemia, the mechanisms responsible for CRF are not yet completely understood. Therefore, CRF may be influenced by multiple possible somatic and psychosocial factors. CRF has been shown as either a short-term side effect of adjuvant cancer therapy or a chronic long-term late effect. Compared with other symptoms, such as pain or nausea, CRF is more distressing and often long lasting, with a strong impact on daily living and quality of life. The concept of fatigue has been widely elaborated and operationalized in different dimensions within the last few decades and specific instruments assessing fatigue in cancer populations have been developed. To support patients and alleviate CRF symptoms various treatment strategies are discussed in this article, including information and counseling, enhancement of activities, exercise and sports therapy, psychosocial interventions as well as pharmacological treatment. In most Western countries, treatment of CRF has been identified as a priority for advancing cancer patient care. This article gives an overview of the concept of CRF, its pathogenesis, assessment and treatment strategies.