The components of the renin-angiotensin system (RAS) in progressive renal disease have been extensively investigated, indicating multiple actions beyond hemodynamic and salt/water homeostasis [1]. Studies in various human diseases and in animal models have shown that angiotensin I-converting enzyme inhibitors (ACEIs) are superior to other antihypertensive agents in protecting the kidney against progressive deterioration, even in conditions without systemic hypertension. The RAS interacts with aldosterone, bradykinin and plasminogen activator inhibitor-1 (PAI-1) with important consequences for kidney function and structure. Inhibition of the RAS could promote remodeling and/or regression of sclerosis by decreased matrix synthesis and augmented proteolysis, the latter contributed to by decreased PAI-1. This review will focus on the effects of the RAS on PAI-1 and fibrosis.