Chronic kidney disease (CKD) will progress to end stage without treatment, but the decline of renal function may not be linear. Compared to GFR and proteinuria, new surrogate markers, such as KIM-1, NGAL, apoA-IV, and soluble urokinase receptor (suPAR), may allow potential intervention and treatment in the earlier stages of CKD, which could be useful for clinical trials. New omic-based technologies reveal potential new genomic and epigenomic mechanisms which appear different from those causing the initial disease. Various clinical studies also suggest that acute kidney injury (AKI) is a major risk for progressive CKD. To ameliorate the progression of CKD, the first step is optimizing renin-angiotensin-aldosterone system (RAAS) blockade. New drugs targeting endothelin, transforming growth factor-β (TGFβ), oxidative stress and inflammatory and cell-based regenerative therapy may have add-on benefit.