Treatment of multiple myeloma (MM) patients has radically changed over the last years following the introduction of next generation proteasome inhibitors (PI) and immunomodulatory derivative (IMiDs). In the last years, one further therapeutic option for MM patients is represented by monoclonal antibodies (MoAbs), that seem to change the paradigm of MM treatment, particularly for heavily pretreated or double refractory to a PI and IMiDs patients. Antibodies have an immune-based mechanism, induce durable responses with limited toxicity and combine well with existing therapies. The therapeutic effects are prevalently obtained by means of antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), complement-dependent cytotoxicity (CDC) and concurrently by the induction of signals on cell effectors. Immunotherapeutic strategies offer a new and exciting approach to target key molecular pathways that continue to be implicated in the survival of malignant plasma cells. These targets include cell surface proteins (CD38, CD138 [SDC1], B cell maturation antigen [BCMA, TNFRSF17]), cytokines that play a role in plasma cell survival and proliferation (interleukin 6 [IL6] and B cell activating factor), signal regulators of bone metabolism (RANKL [TNFSF11], DKK1) and regulators of the immune system (PD-1[PDCD1], PD-L1[CD274]). This article focuses on new MoAbs and related innovative immunotherapeutic modalities currently under investigation in the treatment landscape of MM.