“Enormous progress has been made in the treatment of pediatric cancers over the past several decades,” noted the American Association of Cancer Research in its inaugural AACR Pediatric Cancer Progress Report 2025. The most common cancers among children and adolescents are leukemias, brain and central nervous system tumors, lymphomas, thyroid cancer and germ cell tumors. Pediatric cancers are rare, with about 15,000 diagnoses in 2025. Of note, more than 30 new drugs have been approved for pediatric cancer in the past 10 years. The five-year survival rate for all pediatric cancers combined has increased from 63% in the mid-1970s to 87% during 2015–2021. And pediatric cancer mortality in the United States declined by 57% between 1970 and 2000 and by a further 19% from 2001 to 2023. Challenges include persistent disparities and gaps in knowledge about rare malignancies.