Overall survival from childhood malignancies has dramatically improved, with survival rates now reaching over 70%. Nevertheless, some types of childhood cancer remain a difficult challenge, and for those who survive the burden of treatment can be considerable. The current paradigm for new cancer therapies is to increase our knowledge of the molecular basis of carcinogenesis, followed by the development of cancer-cell specific therapies. Historically, drug development was focused on adult cancers, and the potential efficacy in childhood malignancies was not considered. Recently, a European academic consortium was established, namely 'innovative therapies for children with cancer' (ITCC), to address this unmet need. This initiative is focused on the evaluation of novel agents in pediatric cancer pre-clinical models, and early clinical development of promising new drugs. The number of pediatric patients eligible to participate in such trials is limited, and accurate pre-clinical evaluation may provide evidence-based prioritization for clinical development. Until recently, clinical development of new drugs in childhood cancer was restricted by the limited accessibility of such agents. Recent changes in EU legislation oblige pharmaceutical companies to provide pediatric clinical data for all new drugs relevant to children, including anti-cancer drugs. Pediatric consortiums like ITCC have established networks of expertise with the specific aim of evaluating new drugs for the treatment of childhood cancers. Through proper evaluation in collaborative clinical trials we will learn how best to use these new therapeutic approaches and improve the survival rates and reduce toxicity for children with cancer.