Multidisciplinary collaboration in therapeutic research in childhood cancer has been responsible for enormous improvements in outcomes. Many of the improvements have resulted from large clinical trials carried out in multisite settings through the Children's Oncology Group (COG) and its predecessors, the Children's Cancer Group, the Pediatric Oncology Group, the National Wilms' Tumor Study, and Intergroup Rhabdomyosarcoma Study Groups. Childhood acute lymphoblastic leukemia models the past success of 35 years of randomized clinical trials that resulted in survival rates of around 80%. However more can be done to improve both survival rates and the quality of survival. Areas that can benefit from a transdisciplinary model of research are discussed, as well as challenges to this form of collaboration.