Optimal use of antileukemic agents and stringent application of risk-directed therapy in clinical trials have resulted in steady improvement in the outcome of children with acute lymphoblastic leukemia, with current cure rates exceeding 80% in developed countries. The intensity of treatment varies substantially among subsets of patients, as therapy is designed to reduce acute and long-term toxicity in low-risk groups while improving outcomes in poor risk groups by treatment intensification. Recent advances in genome-wide screening techniques, pharmacogenomic studies, and development of molecular therapeutics are ushering in an era of more refined personalized therapy.