Prostate cancer is the most common cancer among men in the United States. Advanced prostate cancer has a particular propensity to metastasize to bone, where it produces predominantly osteoblastic lesions and local bone formation. The tropism for bone is thought to be due in part to specific interactions between the prostate cancer cells and cells present in the bone environment, particularly the bone marrow endothelial cells and osteoblasts. Such interactions involve numerous signaling pathways that could serve as targets for new therapeutic agents. Because androgen directly influences the proliferation and metastasis of prostate cancer cells, the current first-line treatment for metastatic prostate cancer is androgen deprivation therapy. Subsequent therapies include chemotherapy and radiation therapy. New molecular therapies are being developed to target specific steps in the metastatic process. However, as yet none of these therapies has radically improved survival. Nonetheless, it is hoped that with better understanding of the biology of the disease, combination therapy that addresses multiple pathways that support the progression of prostate cancer in bone could significantly improve the survival and quality of life of men with prostate cancer.