Cancer-related fatigue (CRF) is a highly prevalent and debilitating symptom experienced by most cancer patients during, and often for considerable periods after, treatment. This symptom affects patients' overall quality of life and is characterized by persistent exhaustion and a decreased capacity to perform daily social and cognitive tasks. CRF is also one of the most commonly reported side effects of cancer and cancer treatments, including surgery, chemotherapy, radiotherapy, hormonal therapy, and biologic response modification therapy. Pharmacologic methods for treating CRF are not always reliable, and many patients continue to experience this symptom following pharmacologic interventions. Managing CRF is of importance to oncology researchers and clinical service providers. As of March 15, 2006, 76 National Institutes of Health sponsored studies examining CRF were actively recruiting subjects, and 15% of these studies were being conducted through the National Cancer Institute (NCI) Community Clinical Oncology Program (CCOP). This article will provide a description of-the NCI CCOP, its functions, and a brief overview of ongoing research on CRF both at our institution and other locations across the United States.