Minimal residual disease (MRD) analysis for patients of acute leukemia has evolved as a significant prognostic factor. Based on the MRD results, the cases are risk-stratified after induction chemotherapy, and an alteration in further management is made to yield maximal therapeutic benefits. The two primary methodologies for MRD detection are multi-parameter flow cytometry (MFC) and polymerase chain reaction. MFC identifies the MRD based on characteristic 'leukemia-associated immunophenotypes' on the residual leukemia cells. MRD analysis by MFC is most frequently done at the post-induction stage of treatment and often can achieve a sensitivity of detecting one leukemic cell in 10,000 normal cells, or even higher at times. This review outlines the technical aspects and provides inputs on standard antibody panels used for MRD detection in B-, T-lineage acute lymphoblastic leukemias, and acute myeloid leukemia.