Systemic hypertension complicates the course of most patients with chronic renal failure and accelerates the progression of experimental and clinical glomerular disease. Based on recent experimental studies, it is suggested that at similar levels of systemic hypertension, glomerular injury only develops when pre-glomerular resistances are ineffective, thus allowing the development of glomerular hypertension. The mechanisms by which the hemodynamic stress of elevated intracapillary flows and pressures leads to progressive glomerular damage, particularly to the development of focal glomerulosclerosis is currently unknown. Endothelial cell injury, increased mesangial traffic or trapping of macromolecules and epithelial cell injury, or a combination, appear to occur early, followed by in situ inflammatory and microthrombotic mechanisms. This may explain why various therapeutic approaches, whether dietary or pharmacologic, can have salutory effects despite their diverse mechanisms of action.