Glomerulosclerosis is a general term for scarring of the kidney glomerulus. It cannot be reversed. As glomerulosclerosis accumulates, the diseased kidney progresses to end-stage renal disease. Treatment with inhibitors of the renin-angiotensin system often decreases the rate of progression of glomerulosclerosis in chronic kidney diseases. Although the mechanisms by which these inhibitors mediate their beneficial effects are incompletely understood, it has been suggested that they act, at least in part, by reducing intraglomerular blood pressure and thereby shear stress-induced loss of podocytes, a key component of the glomerular filtration barrier. In this issue of the JCI, Sachs and colleagues provide experimental confirmation of the critical role of tight adhesion of podocytes to the glomerular basement membrane for maintaining glomerular integrity and provide evidence that inhibition of the renin-angiotensin system reduces glomerulosclerosis in animals with less tightly adherent podocytes, presumably by reducing intraglomerular blood pressure.