Treatment of acute myelogenous leukemia (AML) over the past four decades remains mostly unchanged and the prognosis for the majority of patients remains poor. Most of the significant advances that have been observed are in defining cytogenetic abnormalities, as well as the genetic and epigenetic profiles of AML patients. While new cytogenetic and genetic aberrations such as the FLT3-ITD and NPM1 mutations are able to guide prognosis for the majority of patients with AML, outcomes are still dismal and relapse rates remain high. It is thought that relapse in AML is in part driven by minimal residual disease (MRD) that remains in the patient following treatment. Thus, there is a need for sensitive and objective methodology for MRD detection. Methodologies such as multiparameter flow cytometry (MFC), quantitative real-time polymerase chain reaction (RQ-PCR), digital PCR (dPCR), or next-generation sequencing (NGS) are being employed to evaluate their utility in MRD assessment. In this review, we will provide an overview of AML and the clinical utility of MRD measurement. We will discuss optimal timing to MRD measurement, the different approaches that are available, and efforts in the standardization across laboratories.