The prevalence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) are steadily increasing. This phenomenon is in part linked to the aging of the US population, in part to the increasing prevalence of obesity, diabetes and related renal diseases. Some believe that renal ischemia may be a frequent cause of CKD and ESRD, but the prevalence of this condition is difficult to ascertain due to limitations of available diagnostic tools. The current definition of renal ischemia is also ground for confusion. Renal ischemia as a cause of progressive renal disease is commonly defined as a progressive decrease in glomerular filtration rate due to atherosclerosis of the main renal arteries. This definition however, is too restrictive and it does not take into account that functional and anatomical alterations of the renal microcirculation may also lead to progressive renal failure. In this review, we evaluate the clinical and pathophysiological aspects of ischemia-related progressive kidney disease.