The classification of acute myeloid leukemia (AML) is defined by a combination of clinical, morphologic, immunophenotypic and genetic features. This combined approach has been used to improve risk assignment and predict response to therapy. However, it remains difficult to estimate prognosis with precision on the basis of presenting features. To this end, minimal residual disease (MRD) monitoring can provide additional useful information. Flow cytometry allows monitoring of MRD in the majority of patients with AML. It can distinguish leukemic from normal immature myeloid cells by detecting multiple immunophenotypic abnormalities. Contemporary flow cytometers can detect 8 or more markers simultaneously, a feature that increases the reliability and sensitivity of the assay. MRD levels measured by flow cytometry after remission induction chemotherapy are an important indicator of outcome. When measured at subsequent time-points, tracking of MRD may allow timely changes in treatment strategies. MRD is increasingly being used as an inclusion criteria and a response parameter in clinical trials of novel agents. Factors that can impact quality such as sample preparation, choice of fluorochromes and instrument stability will be discussed. Details of antibody panels will be described including markers that can clearly distinguish normal myeloid progenitors from leukemic blast cells.