This chapter discusses how minimal residual disease (MRD) is detected and managed in acute myeloid leukemia (AML) patients. The most commonly used techniques to detect residual leukemia in patients in complete remission (CR) are quantitative PCR (qPCR) and multicolor flow cytometry (MFC). While qPCR techniques have been extensively validated in multicenter efforts, and MRD detection using qPCR targets RNA or DNA sequences, which are derived from fusion genes, mutated genes, or genes overexpressed in AML cells, less formalized testing has been performed with MFC. For all major MRD markers, prognosis has been shown to be affected by the MRD level after the first course of chemotherapy. The applicability of MRD markers varies considerably. The majority of AML relapses occur within the first 2 years from diagnosis. That is not to say that relapse cannot occur later; but, on closer molecular characterization, late relapses will often turn out to be cases of secondary AML.