The detection of very low numbers of leukemic cells persisting after treatment, i.e. the monitoring of minimal residual disease (MRD) is of significant clinical value for children with acute lymphoblastic leukemia (ALL). Particularly, the assessment of early response to remission induction treatment has high prognostic value and enables more reliable definition of low-risk and high-risk patient groups. This forms the basis for treatment modification in new treatment protocols. The predictive value of MRD monitoring is particularly clear after first relapse. It enables recognition of low-risk patients with low MRD levels (probability of relapse-free survival (RFS) of 86%), whereas high MRD levels in high-risk patients are predictive of dismal outcome (probability of RFS of 0%). Moreover high MRD positivity before stem cell transplantation is strongly prognostic of relapse after transplantation.