Multiple myeloma is a clonal disorder of bone marrow plasma cells. Despite the impressive advances in treatment options in the last two decades, myeloma remains incurable. Most of the highly successful recent therapies are immune-based, and it is believed that immunotherapy would continue to push the boundaries of myeloma care well into the future. The very first immunotherapy deployed in the treatment of cancers, including multiple myeloma, was allogeneic stem cell transplantation, and the success of this procedure and that of donor lymphocyte infusions highlighted the potency of cellular therapy. The subsequent introduction of immunomodulatory drugs (like thalidomide, lenalidomide, and pomalidomide), monoclonal antibodies (like daratumumab and elotuzumab), and most recently, chimeric antigen receptor T cells, have effectively established the critical importance of both humoral and cellular immunotherapy in the contemporary management of multiple myeloma. Several other immunotherapies have also entered clinical trials, including bispecific antibodies, antibody-drug conjugates, and checkpoint inhibitors. Most of these therapies target specific antigens expressed by the malignant plasma cell clone, and this chapter will discuss the evidence for the efficacy of these various immunotherapeutic strategies.