The most common cancers, such as those affecting the breast, prostate, and lung have a strong predilection to metastasize to bone. Bone metastasis frequently results in pain, pathologic fractures, hypercalcemia, and spinal cord compression. Pain can have a devastating effect on the quality of life in advanced cancer patients and is a serious complication of cancer. Although significant advances are being made in cancer treatment and diagnosis, the basic neurobiology of bone cancer pain is poorly understood. New insights into the mechanisms that induce cancer pain now are coming from animal models. Chemicals derived from tumor cells, inflammatory cells, and cells derived from bone appear to be involved simultaneously in driving this frequently difficult-to-control pain state. Understanding the mechanisms involved in the pathophysiology of bone cancer pain will improve both our ability to provide mechanism-based therapies and the quality of life of cancer patients.