In this multimodel overview, we have provided the seminal experimental evidence for the crucial contribution of macrophages in the progression of glomerular and interstitial fibrosis. Although all the experimental data provided in this review definitely increase our understanding of the progress of renal disease, we have been mindful to use caution in extrapolating data from animal experiments to the clinical setting (109). In addition, uncertainty still exists as to whether macrophages activation entails a generalized mechanism in which the cells release growth factors and other mediators such as bioactive lipids and nitric oxide simultaneously, or a selective mechanism in which the cells release some but not all macrophage products (110). However, we anticipate that further substantial clinical and experimental observations are on the horizon. Novel therapeutic strategies in these models must be concerned with the prevention of renal macrophage recruitment and/or the suppression of the fibrogenic ability of this pluripotential inflammatory cell.