Growing knowledge of the complexities of the immune system have led to a better understanding of how it can be harnessed for the purpose of anticancer therapy. Moreover, recent success with immunotherapies for solid tumors, combined with novel therapeutic strategies against myeloma, heighten excitement at the prospect of improving clinical outcomes for myeloma by improving antitumor immunity. Increased understanding of myeloma tumor-associated antigens, availability of more potent vaccines, expanded immune-modulating therapies, development of agents that block immune-suppressive pathways, increased sophistication of adoptive cell therapy techniques and capitalization upon standard autologous transplant are all important standalone or combination strategies that might ultimately improve prognosis of patients with multiple myeloma.