Detection of minimal residual disease (MRD) has prognostic value in acute lymphoblastic leukemia and acute myeloid leukemia. Particularly the evaluation of early treatment response has high prognostic value, because this allows identification of true low-risk and high-risk patients, who may profit from treatment reduction or treatment intensification, respectively. Consequently, monitoring of MRD is now being incorporated in many clinical protocols. Analysis of MRD in acute leukemia is currently mainly performed using flowcytometric immunophenotyping, real-time quantitative (RQ-)PCR analysis of fusion gene transcripts, and RQ-PCR analysis of rearranged immunoglobulin and/or T-cell receptor genes. These three techniques differ in their applicability and sensitivity and it should be noted that MRD results obtained by one method cannot yet easily be compared with MRD results obtained by another method. Also between laboratories applying the same method, significant variations in MRD results can be present. Consequently, multicenter clinical studies with MRD-based treatment intervention need standardization of MRD techniques and quality control of MRD results.