Progressive renal disease poses an increasing problem for the medical community. Though the causes of end–stage renal failure are multiple, the histologic pictures of chronic renal disease are remarkably similar being characterized by interstitial infiltration, fibrosis, tubular atrophy and dilatation. This similarity points to a final common pathway. In addition, renal disease often progresses despite elimination or amelioration of the inciting stimulus. This review deals with the pathomechanisms of progressive renal failure proposing a three–step model of fibrogenesis with an induction phase, a phase of inflammatory, and, lastly, a phase of postinflammatory matrix synthesis. The central role of the tubular epithelial cell as a mediator of interstitial inflammation and its participation in matrix synthesis will be discussed particularly. Finally, a brief overview is listed on new therapeutic approaches to limit the progressive nature of fibrogenesis.