Cancer Related Fatigue (CRF) is the most debilitating side effect from cancer and its treatment. The purpose of this project was to evaluate the effectiveness of physical exercise on CRF in cancer patients undergoing radiotherapy with or without chemotherapy. Forty participants were given an option to participate in an exercise regimen (N = 20) or no exercise (N=20) during their radiotherapy. Outcome measures were mean fatigue scores using the Brief Fatigue Inventory survey. There were significance differences (p = .033) found between the exercise and no exercise groups in post-treatment fatigue scores. Within the exercise group, no significant differences (p =.705) were found in fatigue scores from pre-test to post-test. The findings suggest that physical exercise is more effective than no exercise at all during radiotherapy. Health care professionals should integrate exercise interventions into patients' cancer care plan to reduce the impact of CRF on quality of life.