Background: Based upon observations which indicate that chronic intrarenal hypoxia and microvascular obliteration play an important role in the pathogenesis of renal scarring and loss of function, the idea is presented that restoration of kidney structure and function by arresting microvascular drop-out and restoring the interstitial capillary network could be a feasible approach to regeneration of a diseased kidney. This paper addresses the reasoning behind this possibility. Summary: A ‘unifying vasculogenic hypothesis' is discussed which proposes that, in hypoxic nephrons which retain poorly functioning vascular and epithelial elements, the disease process can be slowed or arrested, and nephrons regenerated, by adoptive transfer of endothelial progenitor cells to restore interstitial and glomerular vascular integrity. It is suggested that no other cell types are required to achieve this end. Improved differentiation, proliferation, and function of surviving nephrons could be achieved by restoring adequate oxygen delivery via this approach. Key Messages: It is hypothesized that, to regenerate the function of a chronically diseased kidney, it is not plausible to create new nephrons. Restoration of function of surviving nephrons could be achieved by regeneration of the renal microvasculature alone. Based upon observations that have demonstrated the feasibility of adoptive endothelial progenitor cell transfer into the kidney, this hypothesis is worthy of being tested.