More than 80% of children with ALL are now cured with chemotherapy without need for transplantation. This remarkable progress is the result of serial large-scale randomized clinical trials incorporating improvements in risk group assignment, administration of risk-adjusted therapy and intensified therapy for children with high-risk disease. Despite these advances, significant numbers of children still die of relapsed or refractory ALL, as ALL is the most frequent malignancy of childhood. This review focuses on the appropriate use of transplantation for children with ALL and optimization of transplant procedures to improve survival and reduce late consequences of therapy.