Multiple myeloma (MM) is a clonal plasma cell malignancy affecting a predominantly elderly population. The continued development of newer therapies with novel mechanisms of action has reshaped the treatment paradigm of this disorder in the last two decades, leading to a significantly improved prognosis. This has in turn resulted in an increasing number of patients in need of therapy for relapsed/refractory disease. Immune-based therapies, including monoclonal antibodies, immune checkpoint inhibitors, and most promisingly, adoptive cellular therapies represent important therapeutic strategies in these patients due to their non-cross resistant mechanisms of actions with the usual frontline therapies comprising of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). The anti-CD38 antibodies daratumumab and more recently isatuximab, with their excellent efficacy and safety profile along with its synergy in combination with IMiDs and PIs, are being increasingly incorporated in the frontline setting. Chimeric antigen receptor–T cell (CART) therapies and bi-specific T-cell engager (BiTE) represent exciting new options that have demonstrated efficacy in heavily pretreated and refractory MM. In this review, we discuss the rationale for use of immune-based therapies in MM and summarize the currently available literature for common antibodies and CAR-T therapies that are utilized in MM.