Metastasis is the result of cancer cell adaptation to a tissue microenvironment at a distance from the primary tumor. Metastatic cancer cells require properties that allow them not only to adapt to a foreign microenvironment but to subvert it in a way that is conducive to their continued proliferation and survival. Recent conceptual and technological advances have contributed to our understanding of the role of the host tissue stroma in promoting tumor cell growth and dissemination and have provided new insight into the genetic makeup of cancers with high metastatic proclivity.