Considerable progress has been made in the treatment of acute and chronic leukemias. Remission rates are generally high and cure rates of up to 80% can be achieved in children with acute lymphoblastic leukemia (ALL). However, in many patients the disease will ultimately recur. In most if not all of these patients, relapse is thought to result from subclinical levels of residual leukemia, termed minimal residual disease (MRD). Therefore, the study of MRD holds a significant potential to understand the biology of relapse and remission and to design new therapies to improve the cure rate of patients. A major goal of these studies is to be able and identify patients at a defined risk of relapse which can lead to risk-adapted therapy approaches. Laboratory assays such as polymerase chain reaction (PCR) and multicolor flow cytometry are sensitive enough to detect one leukemic cell in up to 104-105 normal cells and have become ideal tools to monitor MRD. Especially PCR has been used extensively. Although a wealth of data has been generated, some questions remain as to the impact of monitoring MRD on clinical outcome and are the object of this review.