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Cancer-related fatigue (CRF) has often been called the “sixth vital sign” and was the focus of a symposium at the Oncology Nursing Society's 32nd Annual Congress, where nurses discussed CRF's impact on patients. Despite this dialogue, current nursing perspectives and practice still need to be determined. The definition of CRF as a multidimensional symptom will be considered in this article. CRF may create psychological, functional, cognitive, and socioeconomic issues in patients. Challenges for effective management will be considered.