Renal fibrosis is the final pathological process common to any ongoing, chronic kidney injury or maladaptive repair. It is considered as the underlying pathological process of chronic kidney disease (CKD), which affects more than 10% of world population and for which treatment options are limited. Renal fibrosis is defined by excessive deposition of extracellular matrix, which disrupts and replaces the functional parenchyma that leads to organ failure. Kidney's histological structure can be divided into three main compartments, all of which can be affected by fibrosis, specifically termed glomerulosclerosis in glomeruli, interstitial fibrosis in tubulointerstitium and arteriosclerosis and perivascular fibrosis in vasculature. In this review, we summarized the different appearance, cellular origin and major emerging processes and mediators of fibrosis in each compartment. We also depicted and discussed the challenges in translation of anti-fibrotic treatment to clinical practice and discuss possible solutions and future directions.