Today, 80% of paediatric patients with acute lymphoblastic leukaemia (ALL) can be cured. To reduce the rate of relapses, but also to limit treatment morbidity, risk-adapted treatment has been attempted after identifying the most specific prognostic factors. In addition to clinical factors (e.g. age, WBC), the immunophenotype and cytogenetic results, the early in vivo treatment response as determined by cytology had evolved as the most important predictor for relapse. The lack of specificity of most prognostic factors stimulated the search for more relevant parameters. Detection of minimal residual disease (MRD) at defined time points by identifying clone-specific T-cell receptor- (TCR) or immunoglobulin (Ig) gene rearrangements can provide new, highly specific prognostic information which allows definition of new risk groups. The high sensitivity of the method is a prerequisite for applying treatment reduction in patients with fast clearance of leukaemia. Persistent disease is an indication for treatment modification and intensification. Logistics and quality control are demanding but are essential for the introduction of this new technology into clinical practice.