Background: A decreased physical fitness and impaired social functioning has been reported in patients and survivors of childhood cancer. This is influenced by the negative effects of disease and treatment of childhood cancer and by behavioural and social elements. Exercise training for adults during or after cancer therapy has frequently been reported to improve physical fitness and social functioning. More recently, literature on this subject became available for children and young adults with cancer, both during and after treatment. Objectives: This review aimed to evaluate the effect of a physical exercise training intervention (at home, at a physical therapy centre, or hospital based) on the physical fitness of children with cancer, in comparison with the physical fitness in a care as usual control group. The intervention needed to be offered within the first five years from diagnosis. The second aim was to assess the effects of a physical exercise training intervention in this population on fatigue, anxiety, depression, self efficacy, and health-related quality of life and to assess the adverse effects of the intervention. Search methods: For this review the electronic databases of CENTRAL, MEDLINE, EMBASE, CINAHL, PEDro, and ongoing trial registries were searched on 6 September 2011. In addition, a handsearch of reference lists and conference proceedings was performed in that same month. Selection criteria: The review included randomised controlled trials (RCTs) and clinical controlled trials (CCTs) that compared the effects of physical exercise training with no training, in people who were within the first five years of their diagnosis of childhood cancer. Data collection and analysis: By the use of standardised forms two review authors independently identified studies meeting the inclusion criteria, performed the data extraction, and assessed the risk of bias. Quality of the studies was rated by using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria. Main results: Five articles were included in this review: four RCTs (14, 14, 28, and 51 participants) and one CCT (24 participants). In total 131 participants (74 boys, 54 girls, three unknown) were included in the analysis, all being treated for childhood acute lymphoblastic leukaemia (ALL). The study interventions were all implemented during chemotherapy treatment. The duration of the training sessions ranged from 15 to 60 minutes per session. Both the type of intervention, as well as the intervention period, which ranged from 10 weeks to two years, varied in all the included studies. In all included studies the control group received care as usual. All studies had methodological limitations, such as small numbers of participants, unclear randomisation methods, and single-blind study designs in case of an RCT. Cardiorespiratory fitness was studied by the use of the nine-minute run-walk test, the timed up-and-down stairs test, and the 20-m shuttle run test. Only the up-and-down stairs test showed significant differences between the intervention and the control group, in favour of the intervention group (P value = 0.05, no further information available). Bone mineral density was assessed in one study, in which a statistically significant difference in favour of the exercise group was identified (standardised mean difference (SMD) 1.07; 95% confidence interval (CI) 0.48 to 1.66; P value < 0.001). Body mass index was assessed in two studies. The pooled data on this item did not show a statistically significant difference between the intervention and control study group. Flexibility was assessed in three studies. In one study the active ankle dorsiflexion method was used to assess flexibility and the second study they used the passive ankle dorsiflexion test. No statistically significant difference between the intervention and control group was identified with the active ankle dorsiflexion test, whereas with the passive test method a statistically significant difference in favour of the exercise group was found (SMD 0.69; 95% CI 0.12 to 1.25; P value = 0.02). The third study assessed body flexibility by the use of the sit-and-reach distance test; no statistically significant difference between the intervention and control group was identified. One study assessed the effects of an inspiratory muscle training programme aimed to train the lung muscles and increase physical fitness. This study reported no significant effect on either inspiratory or expiratory muscle strength. Two other studies using either knee and ankle strength changes by hand-held dynamometry or the number of completed push-ups (with knees on the ground) and a peripheral quantitative computed tomography of the tibia to determine the muscle mass did not identify statistically significant differences in muscle strength/endurance. The level of daily activity, health-related quality of life, fatigue, and adverse events were assessed in one study only; for all these items no statistically significant differences between the intervention and control group were found. None of the included studies evaluated the outcomes activity energy expenditure, time spent exercising, anxiety and depression, or self efficacy. Authors' conclusions: The effects of physical exercise training interventions for childhood cancer participants are not yet convincing due to small numbers of participants and insufficient study methodology. Despite that, first results show a trend towards an improved physical fitness in the intervention group compared to the control group. Changes in physical fitness were seen by improved body composition, flexibility, and cardiorespiratory fitness. However, the evidence is limited and these positive effects were not found for the other assessed outcomes, such as muscle strength/endurance, the level of daily activity, health-related quality of life, and fatigue. There is a need for more studies with comparable aims and interventions, using higher numbers of participants and for studies with another childhood cancer population than ALL only.