A number of targeted agents under investigation or in development have shown promise in the treatment or prevention of bone metastases. Among them is denosumab (XGEVA, Amgen Inc.), a fully human monoclonal antibody targeting the RANK ligand (RANKL) pathway that was approved on 18 November 2010 in the United States (Amgen XGEVA [denosumab] prescribing information, 2012). Denosumab has been proven superior to zoledronic acid in preserving skeletal function and integrity by preventing skeletal complications among patients with bone metastases from solid tumors. Denosumab has demonstrated prolongation of bone metastasis-free survival in men with castration-resistant prostate cancer and is being investigated for this outcome in women with early-stage breast cancer. Another study is prospectively evaluating a potential prolongation of overall survival with denosumab in patients with metastatic lung cancer. Also currently in development are numerous targeted agents that impact the function of the various growth factors released from the bone matrix that stimulate tumor growth, bone destruction, and lead to bone metastases.