Cardiac fibrosis is a significant global health issue associated with various forms of heart disease. Cardiac fibroblasts (CFs) play a crucial role in maintaining the extracellular matrix (ECM) homeostasis, but upon injury, they transform into myofibroblasts (MFs), contributing to pathological changes such as chamber dilation, cardiomyocyte hypertrophy, and apoptosis, ultimately leading to heart failure. Despite the critical importance of fibrosis in cardiovascular disease, the understanding of CFs remains limited, hindering the development of effective therapies. This review summarizes the current knowledge about the origins and roles of CFs, mediators, and signaling pathways that influence fibroblast function after myocardial injury. It also discusses novel therapeutic strategies aimed at attenuating cardiac fibrosis. Key mediators include transforming growth factor β (TGF-β), the renin-angiotensin-aldosterone system (RAAS), endothelin, RhoA-MRTF-SRF signaling pathway, transient receptor potential channels, and connective tissue growth factor (CTGF). Therapeutic targets such as TGF-β receptor inhibitors, angiotensin receptor blockers, endothelin receptor antagonists, and agents targeting the RhoA-MRTF-SRF pathway are explored for their potential in combating cardiac fibrosis.Cardiac fibrosis is a significant global health issue associated with various forms of heart disease. Cardiac fibroblasts (CFs) play a crucial role in maintaining the extracellular matrix (ECM) homeostasis, but upon injury, they transform into myofibroblasts (MFs), contributing to pathological changes such as chamber dilation, cardiomyocyte hypertrophy, and apoptosis, ultimately leading to heart failure. Despite the critical importance of fibrosis in cardiovascular disease, the understanding of CFs remains limited, hindering the development of effective therapies. This review summarizes the current knowledge about the origins and roles of CFs, mediators, and signaling pathways that influence fibroblast function after myocardial injury. It also discusses novel therapeutic strategies aimed at attenuating cardiac fibrosis. Key mediators include transforming growth factor β (TGF-β), the renin-angiotensin-aldosterone system (RAAS), endothelin, RhoA-MRTF-SRF signaling pathway, transient receptor potential channels, and connective tissue growth factor (CTGF). Therapeutic targets such as TGF-β receptor inhibitors, angiotensin receptor blockers, endothelin receptor antagonists, and agents targeting the RhoA-MRTF-SRF pathway are explored for their potential in combating cardiac fibrosis.