The purpose of this review was to evaluate recent literature on detection methodologies for, and prognostic significance of, measurable ("minimal") residual disease (MRD) in acute myeloid leukemia (AML). There is no "one-fits-all" approach to MRD testing in AML. Most exploited to date are methods relying on immunophenotypic aberrancies (identified via multiparameter flow cytometry) or genetic abnormalities (identified via PCR-based assays). Current methods have important shortcomings, including the lack of assay platform standardization/harmonization across laboratories. In parallel to refinements of existing technologies and data analysis/interpretation, new methodologies (e.g., next-generation sequencing-based assays) are emerging that eventually may complement or replace existing ones. This dynamic evolution of MRD testing has complicated comparisons between individual studies. Nonetheless, an ever-growing body of data demonstrates that a positive MRD test at various time points throughout chemotherapy and hematopoietic cell transplantation identifies patients at particularly high risks of disease recurrence and short survival even after adjustment for other risk factors.