Recent advances in therapy for childhood acute lymphoblastic leukemia have come primarily from the intensive laboratory study of patient's lymphoblasts. DNA-ploidy determination, the analysis of specific chromosomal translocations, and in vitro chemosensitivity studies now facilitate the stratification of risk groups and the prediction of treatment outcome. More is known about the heterogeneity of molecular defects involved in leukemogenesis, and this information is being exploited to devise sensitive tests for minimal residual disease. Conventional chemotherapy of childhood acute lymphoblastic leukemia is associated with adverse neuropsychological sequelae and second malignancies when intensive epipodophyllotoxin therapy is used. Treatment of relapsed acute lymphoblastic leukemia remains problematic. The development of alternative donor marrow sources will expand the role of bone marrow transplantation, which has provided better outcomes for a limited number of patients. We are still waiting to spawn novel therapeutic agents that are more effective and less toxic than present chemotherapy.