The Pediatric Preclinical In Vivo Testing consortium (PIVOT) provides rigorous preclinical testing of novel molecularly targeted agents using in vivo models of pediatric cancer. PIVOT is an extension and expansion of two previous, highly successful NCI programs: Pediatric Preclinical Testing Program (PPTP; 2004-2014) and Pediatric Preclinical Testing Consortium (PPTC; 2015-2021). The objective of the CPRIT (Cancer Prevention and Research Institute of Texas) supported TPC-DTC is to provide reproducible high-quality in vivo data to guide pediatric clinical development of novel agents and combinations. Both initiatives have developed within the context of the Research to Accelerate Cures and Equity for Children Act (RACE for Children Act). For preclinical testing, this necessitates having sufficient models with the appropriate genetic alterations in the context of the appropriate childhood cancer types. The RACE Act requires the FDA to develop a list of molecular targets of known and new drugs/biologics. If agents are determined to be substantially relevant to the growth and progression of pediatric cancer, this may trigger the requirement for pediatric investigations. This expectation applies both to drugs/biologics being developed by Pharma and by academic centers.