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Cancer is a disease predominantly affecting older adults. Cancer fatigue is the most common and often most distressing symptom associated with cancer and its treatment, often persisting months to years after treatment. Untreated cancer fatigue may lead to significant reductions in physical activity, physical functioning, and quality of life and may interfere with patients' adherence to cancer treatment. Physical activity has the strongest supporting evidence as an intervention to reduce cancer fatigue, maintain physical function, and optimize quality of life. This article reviews the literature related to fatigue and physical activity in older adults with cancer. Nine experimental and 10 observational studies that enrolled subjects 65 years or older were synthesized in the review and provided evidence that physical activity may be an effective intervention for cancer fatigue in older adults. The generalizability of the findings to older adults was limited by the poor representation of this age group in the studies. Few studies provided an analysis of age-related effects of physical activity on fatigue, physical function, and quality of life.