The establishment of clinically detectable skeletal metastasis is a multifactorial process. This process can be divided into three general areas of understanding. The first is that of the intrinsic characteristics and properties of the tumor cells, which allow and facilitate their migration from the site of primary neoplasia to the distant host skeleton. Second, there are anatomic considerations of the human body, which influence the distribution of metastatic seeding. Third, there are the considerations of the host organism's biology, including the immune system, the circulatory system, and the affected host skeleton, which hinder and, at times, potentiate the ability of neoplastic cells to establish skeletal lesions.