In recent years, multiparameter flow cytometry (MFC) immunophenotyping has become mandatory in the clinical management of hematological malignancies, both for diagnostic and monitoring purposes. Multiple myeloma (MM) and other clonal plasma cell-related (PC) disorders should be no exception to this paradigm, but incorporation of immunophenotypic studies in the management of patients with PC disorders is still far from being routinely established in many diagnostic flow cytometry laboratories. For clonal PC disorders, MFC is of clear and established clinical relevance in: (1) the differential diagnosis between MM and other PC-related disorders; (2) the identification of high-risk MGUS and smoldering MM; (3) minimal residual disease investigation after therapy; additionally it may also be useful for (4) the definition of prognosis-associated antigenic profiles; and (5) the identification of new therapeutic targets. In this article, we review the clinical value of MFC in the study of PC disorders, with specific emphasis in those areas where consensus exists on the need to incorporate MFC into routine evaluation of MM and other clonal PC-related disorders.