Kidney fibrosis is characterized by accumulation of myofibroblasts, excessive deposition of extracellular matrix in the interstitial space and compromised ability to remove toxins and supply nutrients. Chronic kidney disease (CKD) is the leading cause of kidney fibrosis. CKD manifests as slow, but irreversible damage to renal tissue with scarring, declining kidney function and persistent inflammation and increased oxidative stress. This video provides insight into the roles of TGF-β signaling, diabetic nephropathy, epithelial-mesenchymal transition, serum amyloid A and Src family kinases in CKD, kidney inflammation, and fibrosis. Anti-fibrotic therapies for CKD are urgently needed to improve quality of life and prolong survival.