Survival rates for children with acute lymphoblastic leukemia (ALL) have increased dramatically over the past 4 decades, with 5-year survival rates of > 90% in recent trials. With the increasing number of children and adolescents cured of ALL, identifying and characterizing the occurrence of long-term adverse late effects has become increasingly important. In this young population, successful treatment of ALL is associated with increased risk of adverse outcomes such as late mortality, second neoplasms, chronic health conditions, endocrine dysfunction, and psychological function. Research efforts conducted through large survivor cohorts, such as the Childhood Cancer Survivor Study, are providing new and important insights into the very long-term consequences of ALL therapy, while providing direction for screening recommendations and intervention-based approaches for reducing late morbidity and mortality.