Tumors in bone are usually metastatic, with breast, prostate, and lung tumors accounting for more than 80 percent of clinically manifest lesions. Untreated, such metastases can produce the symptoms that most concern cancer patients--pain, pathologic fractures, and paralysis through epidural cord compression. Recent advances in the understanding of the metastatic cascade and the regulation of bone formation and resorption provide unique therapeutic approaches for prevention and treatment of these lesions. This article reviews the prevalence, distribution, diagnosis, and treatment of metastatic cancer in the skeleton, as well as the processes involved in the development of such metastases, the local mediators responsible for some of the destructive changes in bone, and their pathologic results. In addition to considering some of the conventional therapeutic approaches, a rationale for the use of bone resorption inhibitors, such as the diphosphonates (bisphosphonates), is presented for the prevention and amelioration of the pathologic consequences of skeletal metastases.