Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, accounting for one-third of all cancers occurring in childhood and adolescents. Over the last 3 decades there has been a marked improvement in survival, with 5-year survival rates approaching 80%. With this improvement in survival, increasing attention is now being focused on issues relating to long-term morbidity and mortality associated with the treatments responsible for that increased survival. Because of the young age of these cancer survivors, and thus the potential longevity, the delayed consequences of therapy may have a significant impact on their lives. Long-term sequelae of treatment, such as impaired intellectual and psychomotor functioning, neuroendocrine abnormalities, impaired reproductive capacity, cardiotoxicity, and second malignant neoplasms, are now being reported with increasing frequency in this growing cohort of survivors and knowledge of the late -effects associated with cancer in children and adolescents continues to increase through ongoing research efforts. However, much of the available information relates to outcomes within the first decade following treatment, although information about the longer term outcomes that may occur later in adulthood is emerging as a result of well-conducted, large cohort studies. Through a multi-disciplinary approach to the diagnosis, treatment, and long-term follow-up of pediatric leukemia patients, we can achieve the goal of cure while minimizing the occurrence of long-term adverse outcomes. This review summarizes some of the well-described long-term consequences of therapy among children and adolescents treated for ALL.