When tumors progress to greater malignancy, cells within the tumor develop an increasing ability to detach from neighboring cells and invade through surrounding tissues and tissue boundaries to form new growths (metastasis) at sites distinct from that of the primary tumor. The molecular mechanisms involved in the metastatic process are diverse and not completely understood; however, the processes of cell-cell and cell-extracellular matrix (ECM) adhesion and degradation of the extracellular matrix are accepted as critical. In this chapter, we will focus on the current knowledge of the roles of cell-cell and cell-ECM adhesions in the initiation and maintenance of metastasis at new sites.