Objective To explore the key roles of cancer-associated fibroblasts (CAFs) in the pathogenesis, development, therapeutic resistance, and immune microenvironment modulation of colorectal cancer (CRC). MethodsThrough a systematic review of existing literature, this article summarizes the origin and heterogeneity of CAFs, their mechanisms of action in CRC occurrence and progression, and reviews potential CAF-targeting therapeutic strategies. ResultsCAFs are highly heterogeneous cell populations that drive CRC progression by promoting tumor proliferation, invasion, metastasis, angiogenesis, and inducing therapy resistance. Targeting specific CAF subsets or their key signaling pathways has demonstrated significant tumor-suppressive effects in preclinical studies. ConclusionsAs a crucial component of the tumor microenvironment, CAFs play important roles in the development and therapeutic resistance of CRC. Theoretically, CAF-targeting strategies hold great potential for optimizing CRC treatment. However, translating the therapeutic potential of CAFs into clinical practice still faces numerous challenges, primarily due to limited understanding of their origins, functions, and mechanisms of action. Future research needs to further decipher the subtype-specific functions of CAFs to advance the development of precise treatment strategies.