Despite major progress in the past 40 years, 20% of children with cancer die from the disease, and 40% of survivors have late adverse effects. Innovative, safe, and effective medicines are needed. Although regulatory initiatives in the past 15 years in the USA and Europe have been introduced, new drug development for children with cancer is insufficient. Children and families face major inequity between countries in terms of access to innovative drugs in development. Hurdles and bottlenecks are well known-eg, small numbers of patients, the complexity of developing targeted agents and their biomarkers for selected patients, limitations of US and EU regulations for paediatric medicines, insufficient return on investment, and the global economic crisis facing drug companies. New drug development pathways could efficiently address the challenges with innovative methods and trial designs, investment in biology and preclinical research, new models of partnership and funding including public-private partnerships and precompetitive research consortia, improved regulatory requirements, initiatives and incentives that better address these needs, and increased collaboration between paediatric oncology cooperative groups worldwide. Increased cooperation between all stakeholders-academia, parents' organisations and advocacy groups, regulatory bodies, pharmaceutical companies, philanthropic organisations, and government-will be essential.