Cancer-related fatigue (CRF) is the most common and debilitating side effect of patients receiving treatment of cancer. It is reported that 60% to 100% of patients will develop CRF as a result of the treatment or the cancer itself. The effects last for years posttreatment and lower overall quality of life. The purpose of this integrative review was to determine whether exercise interventions could reduce CRF and improve overall health-related quality of life (HRQOL) among selected cancer patients. Clinical Key, ProQuest Nursing and Allied Health Source, Cochrane Library, Mosby's Nursing Consult, and MEDLINE (Ovid) were the databases searched. Key terms searched were fatigue, exercise, cancer fatigue, holistic, spiritual, quality of life, and prevention. Findings from most studies suggest that exercise can decrease the effects of CRF among cancer patients, leading to an overall improved HRQOL. No negative results on the effects of exercise on CRF were reported. Nurses can be instrumental in developing holistic multidisciplinary exercise programs to assist in the management of CRF and improve HRQOL among cancer patients during and after cancer treatment. Recommendations for future research include the need for larger study sample sizes, a universal definition of fatigue, determination of the best exercise regimens, more consistent fatigue measures to facilitate better comparison across studies, and specifically assess patient improvements in overall mental and spiritual well-being within a holistic framework.