Childhood acute lymphoblastic leukemia is a model in oncology. The outcome was dismal 40 years ago but is now generally excellent, owing to the recent advent of new drugs. These advances were made possible by the creation of specialized units, better supportive care (transfusions, antibiotics and pain control) and intense biological and clinical research coordinated by national and international cooperative groups, allowing the use of available drugs to be optimized. The current aims are to de-escalate treatment for better-defined low-risk groups, and to develop the use of new drugs and targeted therapies for high-risk groups, based on genome-wide analysis of the patient and the leukemic cell.