Minimal residual disease (MRD) in acute myeloid leukemia (AML) can be measured either by flow cytometry to detect leukemic immunophenotypes or by PCR amplification of fusion transcripts, gene mutations and overexpressed genes. Flow cytometry MRD is widely applicable but has an intermediate sensitivity; PCR MRD is highly sensitive but has a restricted applicability. MRD, measured at different time points throughout AML treatment, has proven to powerfully predict the risk of relapse. Acute promyelocytic leukemia, a subtype of AML, represents an excellent example of systematic evaluation and established clinical application of MRD performed by PCR. However, a standardization of MRD techniques, threshold levels, time-points and clinical interventions based on its results is still needed in this field. This article is focused on the current available information on MRD as a prognostic marker in childhood AML.