Cardiac fibrosis is characterized by the accumulation of extracellular matrix proteins in the cardiac interstitium, leading to systolic and diastolic dysfunction in various cardiac pathophysiologic conditions. This review discusses the cellular effectors and molecular pathways involved in the pathogenesis of cardiac fibrosis. Activated myofibroblasts are the primary effector cells, but monocytes/macrophages, lymphocytes, mast cells, vascular cells, and cardiomyocytes also contribute by secreting key fibrogenic mediators. Key mediators include inflammatory cytokines, chemokines, reactive oxygen species, mast cell-derived proteases, endothelin-1, the renin/angiotensin/aldosterone system, matricellular proteins, and growth factors (such as TGF-β and PDGF). Both experimental and clinical evidence suggests that cardiac fibrotic alterations may be reversible. Understanding the mechanisms of cardiac fibrosis is crucial for developing anti-fibrotic treatments for heart disease.Cardiac fibrosis is characterized by the accumulation of extracellular matrix proteins in the cardiac interstitium, leading to systolic and diastolic dysfunction in various cardiac pathophysiologic conditions. This review discusses the cellular effectors and molecular pathways involved in the pathogenesis of cardiac fibrosis. Activated myofibroblasts are the primary effector cells, but monocytes/macrophages, lymphocytes, mast cells, vascular cells, and cardiomyocytes also contribute by secreting key fibrogenic mediators. Key mediators include inflammatory cytokines, chemokines, reactive oxygen species, mast cell-derived proteases, endothelin-1, the renin/angiotensin/aldosterone system, matricellular proteins, and growth factors (such as TGF-β and PDGF). Both experimental and clinical evidence suggests that cardiac fibrotic alterations may be reversible. Understanding the mechanisms of cardiac fibrosis is crucial for developing anti-fibrotic treatments for heart disease.