The high CD38 expression by plasma cells together with the biological functions of CD38 resulted in the development of CD38 antibodies for the treatment of multiple myeloma (MM) patients. The cytolytic activity of CD38 antibodies is mediated by complement-dependent cytoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), direct cell death effects and immunomodulatory effects. CD38 antibodies have demonstrated their clinical benefit as single agent or in combination for the treatment of multiple myeloma patients and will contribute to further improvement in the outcome of MM patients.