Fatigue is one of the most common and debilitating symptoms experienced by patients with cancer. Cancer-related fatigue (CRF) is characterized by feelings of tiredness, weakness, and lack of energy, and is distinct from the "normal" drowsiness experienced by healthy individuals in that it is not relieved by rest or sleep. It occurs both as a consequence of the cancer itself and as a side effect of cancer treatment, although the precise underlying pathophysiology is largely unknown. CRF may be an early symptom of malignant disease and is reported by as many as 40% of patients at diagnosis. Virtually all patients expect fatigue from cancer therapy. Up to 90% of patients treated with radiation and up to 80% of those treated with chemotherapy experience fatigue. CRF continues for months and even years ollowing completion of treatment in approximately one third of the patients with cancer. The impact of CRF on a patient's quality of life (QoL), particularly in relation to physical functioning and the ability to perform activities of daily living, is both profound and pervasive. In addition, CRF is associated with considerable psychological distress and can impose a significant financial burden by limiting a patient's ability to work. These effects can extend to caregivers and family members, who may also have to reduce their working capacity in order to provide additional care for a patient with CRF. This paper examines the prevalence of CRF and explores the impact of this distressing symptom on patients' functioning and QoL. Disclosure of potential conflicts of interest is found at the end of this article.