Highly sensitive methods such as multiparameter flow cytometry and real-time quantitative PCR (RQ-PCR) are increasingly used to monitor minimal residual disease (MRD) and to guide risk-adapted management in acute myeloid leukemia (AML). An independent prognostic utility has been demonstrated for MRD levels obtained by both methods. Multiparameter flow cytometry has been found to be particularly useful for the assessment of early clearance of malignant bone marrow cells and after consolidation therapy. At the latter checkpoint, MRD levels quantitated by RQ-PCR in AML with fusion genes also have the strongest prognostic power. In addition, highly predictive initial expression levels have been identified by RQ-PCR. Both methods are capable of early detection of relapse. By use of all available markers including NPM1 and FLT3 mutations in addition to fusion genes RQ-PCR-based MRD assessment is possible in more than half of patients while multiparameter flow cytometry is applicable to most AML cases. With a sensitivity of 10^–4 (PML-RARA) to 10^–7 (patient-specific primers, FLT3 and NPM1 mutations) RQ-PCR is more sensitive in most cases. Large clinical trials will determine the exact role of immunologic and RQ-PCR-based monitoring of MRD in the therapeutic management of patients with AML.