The last decade has witnessed a huge expansion in research into the cellular component of tumor stroma, especially cancer-associated fibroblasts (CAFs). The role of TME in the outcome of malignant tumors has been well-established over this period. CAFs are predominantly shown by several studies to mainly act as tumor-promoting agents, however, tumor-inhibiting actions are also being validated by several studies though it has a lesser role as compared to the former. Research in this area is facing numerous hurdles, not only because of a lack of precision in identifying fibroblast-specific markers that are not shared by other cell types but also because CAFs have both protumorigenic and antitumorigenic functions. As understanding as well as methods and techniques to classify CAFs is undergoing more refinement, a much better multipronged and “molecularly informed” therapies can be tailored, targeting both the tumor cells and the heterogenous population of CAFs.