Measurable residual disease (MRD, previously termed minimal residual disease) is an independent, post-diagnosis, prognostic indicator in acute myeloid leukemia (AML) that is important for risk stratification and treatment planning, in conjunction with other well-established clinical, cytogenetic, and molecular data assessed at diagnosis. MRD can be evaluated using a variety of multi-parameter flow cytometry (MFC) and molecular protocols but, to date, these approaches have not been qualitatively or quantitatively standardized, making their use in clinical practice challenging. The objective of this work was to identify key clinical and scientific issues in the measurement and application of MRD in AML, to achieve consensus on these issues, and to provide guidelines for the current and future use of MRD in clinical practice. The work was accomplished over two years, during four meetings by a specially designated MRD working party of the European LeukemiaNet (ELN). The group included 24 faculty with expertise in AML hematopathology, molecular diagnostics, clinical trials, and clinical medicine, from 19 institutions in Europe and the USA. The manuscript is dedicated to the memory of our esteemed colleague David Grimwade, a pioneer in the field of MRD in AML, and an active participant in the present work.