Adjuvant radiation therapy in treatment for breast cancer has been shown to improve patient outcomes and reduce mortality rates. However, many patients experience debilitating fatigue as a result. Currently, there are limited treatment options for fatigue in cancer survivors. Options include pharmaceutical agents, psychological interventions, or nutrition strategies, all of which have limited efficacy. Exercise is recommended in survivorship care plans, but it not widely implemented beyond the use of generalized statements or resource guides given to patients. Therefore, the purpose of this study was the examine the impact of an individualized exercise program on fatigue, quality of life, and physical functioning during radiation therapy for breast cancer. This multi-institutional prospective trial evaluated the effects of supervised, individualized exercise therapy in 422 patients undergoing adjuvant radiotherapy for breast cancer. Following a comprehensive fitness assessment and the completion of the Brief Fatigue Instrument (BFI) questionnaire, each participant participated in a 12-week individualized exercise program offered through Maple Tree Cancer Alliance. At its conclusion, the patients repeated the assessment and questionnaire. Individualized exercise had a positive impact on fitness parameters and severity of fatigue. Specifically, cardiovascular endurance, muscular strength, muscular endurance, and flexibility all significantly improved following the exercise intervention (p<0.05). On average, patients fatigue levels decreased by 31.1% (P<0.01). These results signify that fatigue levels are positively impacted by exercise among patients with breast cancer.