The cellular and biochemical mechanisms that direct the destruction of bone at sites of tumor osteolysis are unknown. To better understand the mechanisms through which tumors direct bone resorption, research has focused on developing in vivo and in vitro experimental models that are useful for studying this process. In vivo experimental systems have been developed that permit study of tumor osteolysis from human and murine tumors, and that permit the study of tumors that arise from (sarcoma) or can metastasize (breast cancer) to bone. Recent research has focused on three questions: (1) Are osteoclasts or tumor cells responsible for bone resorption during tumor osteolysis? (2) What are the cellular mechanisms that are responsible for bone resorption during tumor osteolysis, and (3) what are the tumor cell products that regulate the cellular mechanisms that are responsible for tumor osteolysis? It has been determined that osteoclasts are responsible for bone resorption at sites of tumor osteolysis by enhancing the binding of osteoclast to bone, by inducing osteoclastic bone resorption, and by stimulating osteoclast formation. Attempts to identify tumor cell products that regulate these cellular mechanisms are in progress, and findings suggest that production of macrophage colony stimulating factor may be required for tumor osteolysis to occur with some tumors.