Bone metabolism and turnover are strongly altered in multiple myeloma, as a consequence of the proliferation of malignant cells resembling plasmacells in the bone marrow. By both direct or indirect secretion of several molecules, and cell-to-cell interactions, multiple myeloma cells lead to severe and disabling skeletal alterations, such as osteolytic lesions, pathologic fractures, and osteoporosis. In this review, we summarize the studies concerning the soluble molecules which are supposed to have a role in this pathological process. We then consider the substances that, either in serum or urine specimens, can be dosed in the affected patients, thus giving an indirect measure of their altered bone turnover. In the last part of our review, we discuss the potential action of the new anti-myeloma drug bortezomib (Velcade(®), Janssen-Cilag), in opposing and maybe reverting, through a possible direct "proosteoblastic" effect, the deranged bone turnover which characterizes this disabling and unavoidably deathly disease.