Objective The objective of this study was to determine the extent to which self-efficacy mediates the relations between social support and childhood cancer survivors' physical activity (PA). Methods A structured telephone survey was conducted with 105 childhood cancer survivors aged 8-16 years. Participants completed measures assessing their PA as well as proposed predictors of PA including various demographic, medical, cognitive, and social influences. Multiple mediation analyses were utilized to evaluate the relations between social support, cognitive influences, and survivor PA. Results Cognitive influences, including perceived benefits, barriers, and self-efficacy for PA, partially mediated the influence of family and peer support on survivor PA. Self-efficacy emerged as a significant unique mediator, indicating that higher levels of family and peer support are associated with higher levels of survivor PA via increases in survivor self-efficacy. Conclusions Social support has both direct and indirect influences on survivor PA. Indirectly, social support influences PA via survivor self-efficacy. Interventions should target family and peer support as well as self-efficacy to increase survivor PA. Copyright © 2012 John Wiley & Sons, Ltd.