Multiple myeloma (MM) is an incurable B-cell malignancy of terminally differentiated plasma cells. Besides conventional treatments, several targeted therapies are emerging for MM. We review recent developments in monoclonal antibodies (MoAbs) and (radio)immunoconjugates-based targeted immunotherapeutic (serotherapies) strategies, as well as skeletal targeted radiotherapy (STR) in MM. MoAbs-based strategies include the targeting of cytokines and their receptors as well as toxins, drugs or radionuclide delivery to MM cells. Both targeted radioimmunotherapy (RIT) and STR have proved efficient in the treatment of radiosensitive tumours. We conclude that there is a need for more mechanistic investigations of drug action to identify novel therapeutic targets in myeloma cells, as well as in the bone marrow microenvironment.