Chimerism analysis has become an important tool for the peri-transplant surveillance of engraftment. It offers the possibility to realize imminent graft rejection and it can serve as an indicator for the recurrence of the underlying malignant or non-malignant disease. In addition to this analysis, the characterization of residual disease (MRD) prior to and in the course of follow-up post transplant has become an important prognostic factor to highlight patients at highest risk for relapse. Consecutive post transplant MRD monitoring, together with chimerism analysis, allows the detection of impending relapse in a substantial group of children transplanted for acute leukemia. Consequently, these investigations have become the basis for treatment intervention, for example, to avoid graft rejection, to maintain engraftment and to treat imminent relapse by pre-emptive immunotherapy.