Stroma is a supportive framework of tissue, which consists of mixed connective tissue cells (such as fibroblast, immune cell, andendothelial cell) and also an extracellular matrix. A remodeling of the stroma is a physiological process that occurs during wound healing. In many cancers, the stromal remodeling is continuously occurring in response to chronic inflammation. As a result, the desmoplastic reaction or growth of fibrous tissue that similar to “a wound that does not heal” is one hallmark of several solid cancers. The fibroblast in cancer microenvironment exhibits the different characteristics from the normal one; therefore, it is called “cancer-associated fibroblast (CAF)”. There are three proposed origins of CAF; 1) resident fibroblast, 2) bone marrow derived mesenchymal stem cell or 3) cancer cell through the epithelial to mesenchymal transition. Many recent studies indicate that CAF promotes cancer cell properties such as cell proliferation, anti-apoptosis, migration/invasion, metastasis, and drug resistance through the secreted factors. Experimentally in vitro and in the animal model, the characteristics of CAF and normal fibroblast seem to be interchangeable and this would induce cell death, inhibit tumor growth, suppress metastasis and alleviate drug resistance. This might provide the therapeutic opportunities for the adjunct CAF modification and cancer cell eradication that might offer the superior the therapeutic outcome for cancer patients.