Observational findings demonstrating improved survival for younger adults following pediatric, as opposed to adult, acute lymphoblastic leukemia (ALL) regimens have been translated into international, prospective multicenter clinical trials testing the pediatric regimen in young adult ALL. The results of these studies confirm the feasibility of delivering the pediatric regimen in the adult oncology setting and establish the superiority of this approach relative to historical adult cooperative group regimen results. Specific toxicities, including thrombosis, hepatotoxicity, and osteonecrosis, are more prevalent in adults receiving the pediatric regimen relative to young children. Persistent minimal residual disease (MRD) is a strong prognostic indicator in adults receiving the pediatric regimen; sensitive, high-quality MRD evaluation should be performed in all patients receiving these therapies. Incorporation of targeted agents, particularly in the frontline and MRD+ setting, will usher in the next era of the pediatric regimen in adult ALL.