The outcomes for the patients with multiple myeloma (MM) have been improved substantially in both progression-free survival and overall survival in the past decade. Many patients are now achieving a complete response to treatments. Extensive data indicate that the information about minimal residual disease (MRD) can be used potentially as a biomarker to evaluate the efficacy of different treatment strategies instead of overall survival. Consequently, highly sensitive assays have been already used in progress for detection of MRD in the patients with MM, such as multiparameter flow cytometry, polymerase chain reaction(PCR), next-generation sequencing and positron emission tomography/computed tomography. This review presents an overview of the clinical significance of MRD in patients with MM and charactemitics of four detection techniques for MRD.