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Background and Objective: Tumor growth, development, progression, metastasis, invasion and resistivity against drugs solely depend on the recruitment of surrounding cells, extracellular matrix and Tumor Microenvironment (TME). TME is directly as well as indirectly associated with Cancer- Associated Fibroblasts (CAF). The interactions of CAF with tumor surrounding cells, their origination, activation, transformation and ability to recruit other non-tumor cells for the clemency of tumor, are very complex and under active research since long. This study provides an in-depth review of CAF and highlights its potential targets for the regulation of TME as well as discusses current drugs in clinical trials, targeting through CAF. Conclusion: The potential role of CAF in anti-tumor therapy is based on its coherent response against drugs, targeting different tumor sections through these genetically more stable and anti …