Purpose: Childhood cancer survivors (CCSs) are at increased risk for poor health-related quality of life (HRQOL) and chronic health conditions-both of which can be exacerbated by unhealthy lifestyle behaviors. Developing a clearer understanding of the associations between HRQOL, lifestyle behaviors, and medical and demographic variables (e.g., age/developmental stage at time of diagnosis) is an important step toward developing more targeted behavioral interventions for this population. Method: Cross-sectional questionnaires were completed by 170 CCSs who were diagnosed with leukemia, lymphoma, sarcoma, or a cancer of the central nervous system (CNS) and treated at a comprehensive cancer center between 1992 and 2007. Questionnaires addressed weight status, lifestyle behaviors, aspects of HRQOL, and intervention preferences. Results: Adolescent and young adult survivors (AYAs) and survivors of CNS tumors or lymphoma reported significantly (p<.05) poorer HRQOL across multiple domains compared to those diagnosed at an earlier age, survivors of leukemia or sarcoma, and healthy populations. A significant proportion also failed to meet national recommendations for dietary intakes (39-94 %) and physical activity (65 %). Female survivors reported poorer physical functioning and consumed less dietary fiber and fruits and vegetables than did male survivors. They also expressed the strongest interest in participating in diet and exercise interventions. Conclusion: Findings support the premise that females, AYAs, and survivors of cancers of the CNS or lymphoma are "at risk" subgroups within the CCS population for poor dietary practices, sedentary behaviors, and poor HRQOL. Future research should focus on developing diet and PA interventions to improve HRQOL that target these groups. Implications for Cancer Survivors: Greater consideration of the role of gender, developmental stage, and the HRQOL challenges facing CCSs may help researchers to develop targeted behavioral interventions for those who stand to benefit the most. © 2013 Springer Science+Business Media New York.