More than 1.3 million cases of cancer will be diagnosed in 2006 in the United States alone, and 90% of patients with advanced cancer will experience significant, life-altering cancer-induced pain. Bone cancer pain is the most common pain in patients with advanced cancer as most common tumors including breast, prostate, and lung have a remarkable affinity to metastasize to bone. Once tumors metastasize to bone they are a major cause of morbidity and mortality as the tumor induces significant skeletal remodeling, pain and anemia, which reduce the survival and quality of life of the patient. Currently, the factors that drive cancer pain are poorly understood; however, several recently introduced models of cancer pain are not only providing insight into the mechanisms that drive bone cancer pain but are guiding the development of novel mechanism-based therapies to treat the pain and skeletal remodeling that accompanies metatstatic bone cancer. As analgesics can also influence disease progression, findings from these studies may lead to therapies that have the potential to improve the quality of life and survival of patients with skeletal malignancies.