The major clinical manifestation of multiple myeloma is related to the osteolytic bone destruction. The bone disease can lead to pathologic fractures, spinal cord compression, hypercalcemia, and pain. It is also a major cause of morbidity and mortality in these patients. These patients frequently require radiation therapy, surgery and analgesic medications. Bisphosphonates are specific inhibitors of osteoclastic activity, and these agents have been evaluated in myeloma patients with bone disease during the past 15 years. Several large randomized trials have been conducted in myeloma patients also receiving chemotherapy. Orally administered bisphosphonates have shown little ability to slow the development of skeletal complications in these patients. In contrast, more potent intravenous monthly infusions of either pamidronate or zoledronic acid have reduced the skeletal complications among these patients and are now a mainstay of myeloma therapy. A number of other types of new anti-bone-resorptive agents are also in early clinical development.