Multiple myeloma (MM) remains incurable despite important recent advances in treatment. Over the last 2 years, an anti-CD38 monoclonal antibody daratumumab (DARA) has emerged as a breakthrough targeted therapy for patients with MM. Early-stage clinical trials have found DARA to be safe and to have encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) as well as stem cell transplant has already failed. This review discusses the preclinical and clinical development of DARA, its pathophysiological basis, and its prospects for future use in MM.