Examination of the effects of dietary manipulation on progression of chronic renal failure (CRF) has been of interest for two reasons: dietary protein restriction is an effective method of ameliorating uremic symptoms and studies of changes in serum creatinine (and later, creatinine clearance or glomerular filtration rate, showed that the course of renal insufficiency is predictable. Results from studies of patients and animals with CRF suggested that a low-protein, phosphorus-restricted diet could slow the rate of loss of renal function. Animal studies have identified several mechanisms for progressive renal damage. These include glomerular hypertension causing capillary damage, glomerular damage from hypertrophic stimuli or hypermetabolism, calcium-phosphorus deposition and nephrotoxicity of the diet. The scientific basis for these different mechanisms will be discussed and each mechanism will be analyzed in terms of experimental studies in patients with CRF.