Chronic kidney disease has a continuously increasing prevalence, associated with multiple comorbidities, that in an increased proportion of patients shows a progressive evolution. Knowing the factors involved in the progression of the chronic kidney disease can impose different therapeutic strategies. The final common pathway for almost all forms of renal disease is renal fibrosis. In order to better understand the progression of chronic kidney disease, it is mandatory to present the mechanisms of fibrogenesis, both at glomerular and at the tubulo-interstitial level, and also to find out which treatment targets can be used in order to prevent or reverse this process. After showing data regarding fibrosis, the following chapters will present the main factors involved in the progression of renal disease: arterial hypertension and the renin- angiotensin- aldosterone system, proteinuria, metabolic disorders, anemia, smoking, salt intake and the protective effect of alkali therapy. For an evidence- based approach the results from the main clinical trials that involve these progression factors are also be briefly presented.