Improvement in therapies for childhood acute lymphocytic leukemia has resulted in cure for the majority of young people with this disease. Recent therapeutic advances have focused on testing more extensive treatments for cases with adverse clinical/biologic features, or pharmacologic studies to maximize dose intensity. The latter includes a trial of alternating high-dose intravenous methotrexate with high-dose intravenous 6-mercaptopurine given for the first year postremission in an attempt to circumvent the patient's natural variability of absorption and metabolism of these drugs. Patients with acute myeloid leukemia continue to fare much worse and only one in three are long-term survivors. Acute myeloid leukemia therapies emphasize the use of intensive toxic courses of cytarabine, etoposide, and an anthracycline to cytoreduce the leukemic clone. Acute progranulocytic leukemia, however, now appears to be responsive in vitro to the differentiation agent all-trans retinoic acid. For this disease, complex responses are now obtained without the use of conventional antineoplastics.