Introduction: Immunotherapy has emerged as a major class in the therapeutic arsenal of multiple myeloma. Cell-based immunotherapy (CAR T-cells) and monoclonal antibody-based immunotherapy (naked monoclonal antibodies, antibody-drug conjugates, and bispecific T-cell engagers) are the two cornerstones of this novel approach for myeloma patients. Among numerous targets evaluated in the previous decade; CD38, SLAMF7, and, more recently, BCMA stand as the most promising. Areas covered: This review presents and discusses the currently available data regarding monoclonal antibodies in the treatment of multiple myeloma. Expert opinion: Anti-CD38-naked monoclonal antibodies have become a standard-of-care in multiple myeloma, greatly improving the depth and duration of response when combined with conventional therapy. Elotuzumab is approved in the relapse setting in combination with pomalidomide and maybe an interesting option in patients whose disease became refractory to anti-CD38 monoclonal antibodies. Anti-BCMA drug conjugates and bispecific T-cell engager antibodies are promising new molecules in the multiple myeloma armamentarium.