Children with cancer and their families use complementary and alternative medicine (CAM) to reduce symptoms, cope with life-threatening illness, and improve overall well-being. Despite numerous published surveys on the use of CAM in pediatric oncology, few studies have tested CAM therapies for safety and efficacy. A growing body of literature in adult oncology provides evidence for the role of CAM to help manage symptoms and reduce distress. Translating this research to children requires studies with new models that address family roles and include measurement of outcomes relevant to children’s developmental stages and unique responses. One of the limitations in pediatrics is the small samples available to single institutions. Conducting clinical trials through the cooperative group mechanism is one way of obtaining sufficient sample sizes to determine effectiveness and safety of CAM therapies. This article summarizes research to date and describes a beginning approach to measuring outcomes of supportive CAM therapies in children with cancer.