Progression of chronic kidney disease (CKD) involves the recruitment and engagement of cellular processes originating in specific compartments of the kidney on the one hand and biochemical pathways of cell injury that contribute to these processes on the other hand. Many of these processes possess the capacity to ramify broadly beyond the compartment where they initially arose. It is this essential consideration that contributes so fundamentally to the increasing loss of functional nephrons and the progression of CKD. A number of different biochemical pathways contribute to CKD progression: angiotensin II induces TGF-β1 and the consequent elaboration of extracellular matrix; angiotensin II also induces oxidative stress which itself can upregulate TGF-β1 in vicinal cells and thus the propagation of a fibrosing response. This lack of containment of compartmental processes, and this versatility of injurious biochemical pathways, not only underlies the pathogenesis of CKD but also holds substantial therapeutic significance. Namely, the best hope for retarding or preventing the progression of CKD resides in a combined, multipronged therapeutic approach that interrupts these processes and pathways at separate and several steps.