Obstruction of the upper urinary tract poses a significant clinical challenge to the urologist, and the cascade of renal cellular and molecular events triggered by upper urinary tract obstruction result in a progressive, and eventually permanent, loss in renal function. These pathological changes include the development of renal fibrosis, tubular atrophy, interstitial inflammation, and apoptotic renal cell death. A myriad of cytokines and growth factors have been identified as major contributors to obstruction-induced renal fibrosis and apoptotic cell death, including transforming growth factor-beta1, angiotensin II, nuclear factor-kappaB, and tumor necrosis factor-alpha. This review examines the role of these mediators in obstruction-induced renal injury.