ABSTRACT The Childhood Cancer Survivor Study (CCSS) is a multi-institutional, multi-disciplinary collaborative research resource established to systematically evaluate long-term outcomes among children diagnosed with cancer who survived five or more years from diagnosis. With the recent successful expansion of the cohort to include survivors diagnosed and treated over three decades (1970-1999), the CCSS is the world's largest established open resource for survivorship research with 35,923 eligible survivors available for investigation of late mortality, and 24,368 participants who have contributed health-related and quality of life outcomes. The resource includes comprehensive annotation of treatment exposure, ongoing longitudinal follow-up and an established biorepository, from which genotyping (SNP array) and sequencing (whole exome) of almost 6,000 survivors will be available for investigators for identification of genetic susceptibility for disease- and treatment-induced late effects. Extensive use by the research community has resulted in: 264 published or in press manuscripts now cited over 12,600 times; 229 presented abstracts; 42 investigator-initiated grants, totaling $37.1 million in funding; utilization by a diverse group of 673 investigators; training of 63 young investigators; conduct of six randomized trials; increased knowledge to inform exposure-based clinical care guidelines; and a highly successful model for multiple national and international collaborative initiatives of pediatric cancer survivorship research. During the next five years, activities will focus on maintaining, enhancing and promoting use of this singular resource. The overarching goal of the CCSS resource is to increase the conduct of innovative and high impact research related to pediatric cancer survivorship.