Transforming growth factor β (TGF-β) is a central mediator of fibrogenesis, playing a crucial role in the pathogenesis of fibrotic diseases. TGF-β is upregulated and activated in fibrotic conditions, modulating fibroblast phenotype and function, and promoting matrix preservation. The canonical ALK5/Smad3 pathway is involved in fibrosis, while Smad-independent pathways may regulate Smad activation and directly transduce fibrogenic signals. TGF-β's profibrotic actions are partly mediated through the induction of Connective Tissue Growth Factor (CTGF). Given its essential role in fibrosis, TGF-β has emerged as a promising therapeutic target. However, concerns about potential side effects due to TGF-β's pleiotropic and multifunctional effects, including its role in tissue homeostasis, immunity, and cell proliferation, highlight the need for careful consideration in clinical applications. This minireview summarizes the role of TGF-β signaling pathways in the fibrotic response, emphasizing the importance of both Smad-dependent and Smad-independent pathways in fibrosis.Transforming growth factor β (TGF-β) is a central mediator of fibrogenesis, playing a crucial role in the pathogenesis of fibrotic diseases. TGF-β is upregulated and activated in fibrotic conditions, modulating fibroblast phenotype and function, and promoting matrix preservation. The canonical ALK5/Smad3 pathway is involved in fibrosis, while Smad-independent pathways may regulate Smad activation and directly transduce fibrogenic signals. TGF-β's profibrotic actions are partly mediated through the induction of Connective Tissue Growth Factor (CTGF). Given its essential role in fibrosis, TGF-β has emerged as a promising therapeutic target. However, concerns about potential side effects due to TGF-β's pleiotropic and multifunctional effects, including its role in tissue homeostasis, immunity, and cell proliferation, highlight the need for careful consideration in clinical applications. This minireview summarizes the role of TGF-β signaling pathways in the fibrotic response, emphasizing the importance of both Smad-dependent and Smad-independent pathways in fibrosis.