Metastatic disease is the most lethal aspect of human malignancies, making the understanding and continued research into the process of metastasis a crucial step in treating cancer. The lethality of malignant neoplasms is attributable directly to the development of secondary growths in organs often at a distance from the primary tumor mass. While most primary tumors are treatable and manageable by local resection or irradiation, disseminated cancer cells are often immune to our methods of treatment. Few therapeutic options for patients have demonstrated potential in curing metastatic disease. The molecular mechanisms underlying site-specific metastasis and the factors mediating tumor cell homing remain largely unknown. In this introductory chapter, the metastatic cascade will be reviewed, with emphasis on the individual steps of the metastatic process and the routes of cell dissemination. In addition, the molecular mechanisms driving site-specific metastasis and tumor cell homing to specific sites will be discussed.