The cure rate for childhood acute lymphoblastic leukemia has improved remarkably over the past four decades to over 80% today.This improvement can be traced from the empiric testing of chemotherapeutic agents in the context of multi-institutional protocols, pre-symptomatic treatment of the central nervous system, further intensification of therapy and the use of risk adapted treatment stratification.In spite of these substantial gains, two major issues remain.First, many children are now over-treated and are thus exposed to short and long term side effects.Second, one in five children will relapse and their prognosis is poor even with aggressive retrieval strategies.Given the frequency of ALL compared to other childhood tumors, more children die from ALL each year than any other tumor.