Over the last 20 years, the rate of long-term disease-free survival of childhood acute lymphoblastic leukemia increased from less than 1 to 60 per cent. Strategies for disease control include (1) intensive multiagent induction to rapidly decrease the tumor burden and minimize the chance of emergence of a resistant population of cells, (2) restoration of normal hematopoiesis as soon as possible to reduce the period of pancytopenia, (3) meticulous supportive care, (4) prevention of sanctuary disease, and (5) therapy tailored to the potential risk of relapse as predicted by the prognostic factors of the patient. Further progress must be made in identifying prognostic factors, preventing and treating relapse, finding novel modalities of therapy, and delineating and minimizing long-term side effects.