By the time of diagnosis, primary neoplasms are biologically heterogeneous and contain subpopulations of cells with different metastatic potentials. The pathogenesis of a metastasis consists of many sequential steps that must be completed to produce clinically relevant lesions. During any of these steps, tumor cells interact with host factors in the microenvironment that the tumor cells can usurp. Treatment of metastasis can be directed against tumor cells and/or microenvironmental factors that support tumor growth, such as tumor-associated blood vessels.