Achieving lower morbidity and higher survival rates in the treatment of childhood leukemia has been a paradigm of success in modern oncology. However, serious long-term health complications occur in very large populations of childhood leukemia survivors, in the case of both acute lymphoid leukemia and acute myeloid leukemia (AML). Additionally, 15% of acute lymphoid leukemia patients have treatment failures, and rates are even higher in childhood AML. In the last few decades, as a result of well-tested experiments that statistically analyzed treatment cohorts, new agents have emerged as alternatives or supplements to established treatments, in which high survival and/or less morbidity were observed. This review provides an overview of better practice in the treatment of childhood leukemia.