Background: Fatigue is one of the most distressing and prevalent symptoms reported by pediatric oncology patients. With the increase in cancer survival rates, medical teams have focused on methods that control cancer-related fatigue in children during the disease and its treatment in order to increase the quality of life for these patients. Aim: The objective of this systematic review was to synthesize the best available evidence concerning the effectiveness of nonpharmacological interventions for fatigue in children and adolescents with cancer. Methods: The search strategy was designed to retrieve studies published between 1960 and 2010 in either English or Chinese. This review included randomized controlled trials and quasi-experimental studies. The studies that were selected for retrieval were assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical-appraisal instruments. Results: The review included six studies, and the meta-analysis revealed a statistically significant effect of exercise interventions in reducing general fatigue (effect size = -0.76; 95% CI [-1.35, -0.17]) in children and adolescents with cancer. Conclusions and Implications: The review provides an evidence-based guide to future priorities for clinical practice. Exercise interventions could reduce the levels of general fatigue in children aged 6-18 years. In particular, exercise interventions for fatigue are feasible and safe.