Most colorectal cancer (CRC) patients die as a result of metastasis. Neither conventional chemotherapy nor current targeted therapies offer significant benefits once the disease has spread to distant organs. Furthermore, current CRC staging based on histopathology and imaging has a limited ability to predict the evolution of the disease. We have recently discovered that vast majority of genes that distinguish poor prognosis CRC subtypes are expressed by cancer-associated fibroblasts rather than by epithelial tumor cells. We showed that metastasis relies on a tumor cell non-autonomous program driven by TGF-beta in the tumor microenvironment. Here I will discuss our latest data on how stromal cells help disseminated tumor cells evade the attack of the immune system and the design of new therapeutic strategies based on targeting the tumor microenvironment.