Tumors are unorganized organs that contain many different cell types that communicate with cancer cells (Kalluri NRC 2006). The central goal of our laboratory is to evaluate the role of these non-cancer cells in cancer progression and metastasis. Cancer progression significantly depends on the influence of many different host cells. Whether such host responses are recruited to control cancer progression or further aid in tumor growth (or both) is still unclear. This lecture will highlight the role of extra-cellular matrix, angiogenesis, and mesenchymal cells in cancer progression and metastasis, and discuss treatment strategies.