Bone metastases have a major impact on morbidity and on mortality in cancer patients. Despite its clinical relevance, metastasis remains the most poorly elucidated aspect of carcinogenesis. Different pathways or molecules such as RANK/RANKL/OPG, cathepsin K, endothelin-1, Wnt/DKK1 and Src have recently emerged as potential targets, and preclinical and clinical trials are now underway. The results from clinical trials indicate the importance of treating and preventing bone metastases in many different cancer populations.