Carcinoma of the prostate (CaP) is the most common malignancy in older men in the United States. In 2002, more than 200,000 cases of CaP were diagnosed and an estimated 32,000 Americans died of this cancer (Jemal et al., 2002). Most of the devastating effects of prostate cancer can be attributed to its tendency to metastasize to bone. At the time of clinical presentation, 8% of Caucasian-Americans and 14% of African-Americans already have bone metastasis (Coffey, 1993; Whitmore, 1990), and bone metastases will develop in the majority of patients with recurrent hormoneindependent CaP. Bone metastases are a major cause of morbidity in patients with advanced CaP; major clinical features of bone metastases are intractable bone pain, fracture, spinal cord compression and eventually wasting and death. While the biology of the primary tumor has been intensively studied, the special aspects of CaP bone metastases that lead to abnormal bone growth not ordinarily seen in any other cancers are not extensively documented in the literature. In this chapter, we review the detection of CaP metastases, the predilection of CaP to spread to bone, the main phenotypic features of CaP in bone, and the characterization of the histological “osteoblastic” bone response. We conclude with a brief description of our osteoblastic xenograft model and comparison of this model to clinical bone metastases.