Chronic Kidney Disease (CKD) is a progressive condition characterized by decreased kidney function, tubular injury, oxidative stress, and inflammation. The etiology involves dysregulated signaling pathways, particularly the transforming growth factor (TGF)-β, which promotes the transdifferentiation of renal tubular epithelial cells into mesenchymal cells, leading to irreversible kidney injury. Current therapies, such as renin-angiotensin blockers, mineralocorticoid receptor antagonists, and sodium/glucose cotransporter 2 inhibitors, aim to delay progression. Newer antifibrotic agents and therapeutic targets, including small interfering RNAs and stem cell-based therapeutics, are under investigation. The review covers clinical evaluation methods, imaging modalities, biomarkers, and potential therapeutic agents for fibrosis in CKD. It also discusses the pathophysiology of fibrosis, including the fibrotic niche, dysregulation of TGF-β/Smad signaling, and the role of diabetes, epithelial-mesenchymal transition, and macrophage infiltration. Finally, it explores nephroprotective drugs currently in use and antifibrotic drugs in clinical trials, highlighting the need for further research to avoid dialysis and kidney transplantation.Chronic Kidney Disease (CKD) is a progressive condition characterized by decreased kidney function, tubular injury, oxidative stress, and inflammation. The etiology involves dysregulated signaling pathways, particularly the transforming growth factor (TGF)-β, which promotes the transdifferentiation of renal tubular epithelial cells into mesenchymal cells, leading to irreversible kidney injury. Current therapies, such as renin-angiotensin blockers, mineralocorticoid receptor antagonists, and sodium/glucose cotransporter 2 inhibitors, aim to delay progression. Newer antifibrotic agents and therapeutic targets, including small interfering RNAs and stem cell-based therapeutics, are under investigation. The review covers clinical evaluation methods, imaging modalities, biomarkers, and potential therapeutic agents for fibrosis in CKD. It also discusses the pathophysiology of fibrosis, including the fibrotic niche, dysregulation of TGF-β/Smad signaling, and the role of diabetes, epithelial-mesenchymal transition, and macrophage infiltration. Finally, it explores nephroprotective drugs currently in use and antifibrotic drugs in clinical trials, highlighting the need for further research to avoid dialysis and kidney transplantation.