Chronic kidney diseases share common pathogenic mechanisms that, independently from the initial injury, lead to glomerular hyperfiltration, proteinuria, and progressive renal scarring and function loss. Inhibition of the renin angiotensin system (RAS) has been consistently found to reduce or halt the progressive deterioration of renal function through reduction of blood pressure and proteinuria, the two main determinants of renal function decline. In few instances, RAS inhibition may even promote amelioration of the glomerular filtration rate. Animal data suggest that chronic therapy with angiotensin-converting enzyme inhibitors or angiotensin II receptor type I blockers promotes regression of glomerulosclerosis, even in later phases of the disease. In humans, studies investigating the effect of angiotensin II inhibition on renal structural changes have shown inconsistent results, possibly due to small numbers and/or short duration of follow-up. Whether regression of glomerulosclerosis relies on a direct regenerative effect of RAS inhibition or on spontaneous kidney self-repair after the injury has been removed is still unknown. Improved understanding of mechanisms that promote renal regeneration may help in designing specific therapies to prevent the development of end-stage renal disease. This is a desirable goal, considering the economic burden of chronic kidney diseases and their effect on morbidity and mortality.