Angiotensin II blockade has become a standard anti-fibrotic therapy in renal diseases because it slows progression to end-stage renal disease. However, current data support the notion that angiotensin II blockade alone cannot stop progressive fibrotic disease. Of an increasing number of therapies showing efficacy in animal studies, antibodies to transforming growth factor beta are the most thoroughly studied and are likely to be effective in human clinical trials. However, hints exist in the literature suggesting that no single agent will effectively halt renal fibrosis and that combinations of agents will be required.