Purpose of review: There is new and emerging evidence that renal vascular changes contribute to progressive renal disease and that alteration of vascular endothelial growth factor might play an important role in modulating microvascular loss or macrovascular remodeling in the kidney. Recent findings: Microvascular endothelial loss both in glomerular and peritubular capillaries of progressive renal disease is directly linked to impaired blood flow, the development of renal ischemia and scarring. Vascular endothelial growth factor is a proliferative survival factor for endothelial cells, which could preserve stressed endothelium or stimulate angiogenesis, stabilize renal function and slow histologic progression as shown in different animal models of progressive renal disease. However, there has been some evidence for the mitogen playing a role in the development and progression of atherosclerosis via a mechanism that amplifies the inflammatory reaction. Whether vascular endothelial growth factor is detrimental in early stages of diabetic nephropathy or other renal conditions is not yet clearly answered. Summary: Despite dramatic progress in current knowledge of vascular biology in progressive renal disease, there are still controversies about the mechanism by which vascular endothelial growth factor works in the kidney in different conditions and at different time points. We suggest it is now time to think of integral effects of this angiogenic factor as a new player in renal fibrosis with its potential therapeutic implication.