Tumors cause multiple effects on the skeleton and on calcium homeostasis, but they do so in specific patterns which are becoming better defined as the mediators responsible become more fully characterized. Metastatic bone disease occurs in the majority of patients with advanced cancer, and is particularly frequent in breast, lung and prostate cancers, which are the most common of all human tumors. Approximately 1,000 000 people die each year in Western Europe and the United States from these three malignancies, and the majority of these people have bone metastases. Bone is the third most common site of metastatic disease in tumors of all types and the second most common in breast and prostate cancer. In this review, the role of the tumor peptide parathyroid hormone-related peptide (PTH-rP) in the effects of cancer on the skeleton will be discussed.