Bone metastasis is a leading cause of morbidity in cancer patients. Bone metastasis involves a complex series of biologic events but is ultimately dependent on cancer-mediated bone resorption. Recent advances have established a critical role for resident osteoclasts in this process. Furthermore, the paracrine interactions between cancer cells, resident stromal cells and osteoblasts, and cells in the osteoclast lineage have been defined along with the biologic mediators of these important interactions. These advances have provided novel targets to inhibit tumor-mediated bone resorption and have the potential to markedly decrease the morbidity of terminal cancer. (C) 2000 Lippincott Williams and Wilkins, Inc.