The articles selected in this review highlight some advances in the use of the "old standards" methotrexate and 6-mercaptopurine for the treatment of children with acute lymphoblastic leukemia, especially the laboratory studies, which may allow a "pharmacologic phenotyping" to identify children most likely to relapse. In addition, we review the use of "newer" drugs (epipodophyllotoxins), which may be effective but are also associated with high morbidity (ie, secondary acute myeloid leukemia). As a second issue, "dose intensity" and the use of high-dose chemotherapy followed by bone marrow transplantation will be challenged, especially in light of peripheral stem cell harvest and the use of growth factors.