After damage the kidney has the ability to repair itself. With mild injury this repair can result in the return to a structural and functional state that is indistinguishable from normal. However, when the repair is more severe or is superimposed on baseline kidney abnormalities, the repair process can lead to fibrosis, which can facilitate progression to chronic kidney disease. Epidemiological studies now show that patients who have had acute kidney injury have a marked increase in their risk for the development of end-stage renal disease. Recent data have redefined the role of the surviving epithelial cells in fibrosis and attribute myofibroblast expansion to perivascular and interstitial fibroblasts. After severe injury, the proximal tubule cellular response is impaired with its proliferative response altered due to cell cycle arrest at the G2/M phase of the cell cycle, resulting in generation of profibrotic factors including cytokines, growth factors and matrix proteins.