Abstract: Multiple myeloma (MM) is a malignant proliferative disease of plasma cells, ranking as the second most common hematologic tumor. Although the use of proteasome inhibitors and immunotherapeutic regimens has improved the prognosis of patients with MM, it remains incurable in most patients, mainly because of the eventual development of drug resistance in MM cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells causing significant suppression of the T-cell immune response. They arise from bone marrow myeloid progenitor cells that are blocked from differentiation and promote MM development by resisting immune destruction. Recent studies indicate that MDSCs stimulate MM cell proliferation, inducing drug resistance and metastasis. In this paper, we review multiple mechanisms exhibited by MDSCs in MM pathogenesis and discuss the feasibility and challenges of current therapeutic strategies targeting MDSCs, aiming to provide pertinent references regarding MM treatment.