Fibrosis, or scarring, is a pathological feature of many chronic inflammatory diseases, characterized by the accumulation of excess extracellular matrix components. The process can lead to organ malfunction and death if highly progressive. Key components of both innate and adaptive immune responses contribute to fibrosis by regulating the differentiation, recruitment, proliferation, and activation of extracellular matrix-producing myofibroblasts. This review discusses the mechanisms and pathways of fibrosis, highlighting potential therapeutic targets. Distinct triggers, such as genetic disorders, infections, toxins, and chronic inflammation, can initiate fibrosis. The coagulation response, inflammatory myeloid cells, and innate inflammatory mediators like TNF-α and IL-1β play crucial roles in the progression of fibrosis. TGF-β1, a multifunctional cytokine, has both anti-inflammatory and profibrotic activities. Alternatively activated M2 macrophages can suppress fibrosis by inhibiting ECM synthesis by myofibroblasts. Adaptive immunity, particularly T(H)17 and T(H)2 responses, also contributes to fibrosis through the production of proinflammatory cytokines. Intrinsic, autocrine, and epigenetic mechanisms, such as Wnt-β-catenin signaling and telomere shortening, further perpetuate fibrosis. MicroRNAs (miRNAs) regulate fibroblast growth and activation, making them potential therapeutic targets. Therapeutic strategies targeting myofibroblasts, the TGF-β pathway, and proinflammatory pathways show promise, but a multipronged approach may be necessary to effectively treat fibrosis.Fibrosis, or scarring, is a pathological feature of many chronic inflammatory diseases, characterized by the accumulation of excess extracellular matrix components. The process can lead to organ malfunction and death if highly progressive. Key components of both innate and adaptive immune responses contribute to fibrosis by regulating the differentiation, recruitment, proliferation, and activation of extracellular matrix-producing myofibroblasts. This review discusses the mechanisms and pathways of fibrosis, highlighting potential therapeutic targets. Distinct triggers, such as genetic disorders, infections, toxins, and chronic inflammation, can initiate fibrosis. The coagulation response, inflammatory myeloid cells, and innate inflammatory mediators like TNF-α and IL-1β play crucial roles in the progression of fibrosis. TGF-β1, a multifunctional cytokine, has both anti-inflammatory and profibrotic activities. Alternatively activated M2 macrophages can suppress fibrosis by inhibiting ECM synthesis by myofibroblasts. Adaptive immunity, particularly T(H)17 and T(H)2 responses, also contributes to fibrosis through the production of proinflammatory cytokines. Intrinsic, autocrine, and epigenetic mechanisms, such as Wnt-β-catenin signaling and telomere shortening, further perpetuate fibrosis. MicroRNAs (miRNAs) regulate fibroblast growth and activation, making them potential therapeutic targets. Therapeutic strategies targeting myofibroblasts, the TGF-β pathway, and proinflammatory pathways show promise, but a multipronged approach may be necessary to effectively treat fibrosis.