Abstract: In the past decade, outcomes for patients with multiple myeloma (MM) have improved substantially with the clinical appli cation of novel agents. However, the primary hurdle in the path to curing MM is minimal residual diseases (MRDs), which play a critical role in either progression-free survival or overall survival. A better definition of MRD will aid in tailoring MM therapy further in view of the clonal heterogeneity and genomic instability, and overcome patients' ineffective immune surveillance. MRD analysis can define the logical endpoint for maintenance therapy; in addition, it also aids in providing better clinical endpoints for studies. However, until now, all techniques have flaws in the detection of MRD in the fields of standardization, universal availability, or proper accuracy. This review provides an overview of the advantages and disadvantages of various techniques for MRD detection in patients with MM, including flow cytometry and several molecular techniques, and discusses the direction of its future improvements.