Numerous randomized controlled trials have been conducted to determine efficacy of exercise on cancer-related fatigue. However, many trials lacked sufficient power to demonstrate significant differences, and little is known about how the effect of exercise differs depending on patient- and intervention-level characteristics. A meta-analysis was performed to determine whether exercise reduces fatigue compared with usual care or nonexercise control intervention in patients with cancer. The authors searched Ovid MEDLINE, EMBASE, PsycINFO, The Cochrane Central Register of Controlled Trials, and CINAHL. Two authors independently extracted the data. Randomized controlled trials comparing exercise with control intervention in cancer patients in which fatigue was quantified were eligible. Seventy-two randomized controlled trials were identified, 71 in adults and 1 in children. Exercise had a moderate effect on reducing fatigue compared with control intervention. Exercise also improved depression and sleep disturbance. Type of exercise did not significantly influence the effect on fatigue, depression, or sleep disturbance. Exercise effect was larger in the studies published 2009 or later. There was only one pediatric study. The results of this study suggest that exercise is effective for the management of cancer-related fatigue.