The aim of this study was to analyze the factors affecting chronic renal insufficiency (CRI) progression at diagnosis (markers of progression), their spontaneous or therapy-induced behavior, and their relationship to CRI progression during follow-up. The underlying disease is the 'determinant factor' of progression and although clinical trials usually report crude cumulative renal survival without taking into account concomitant risk factors, it is known that diabetic nephropathy, polycystic kidney disease, and glomerulonephritis are more progressive than nephroangiosclerosis and interstitial nephropathy. Among the 'effect modifiers,' the baseline level of renal function, hypertension, and proteinuria are the most important. The adverse synergistic effects of proteinuria and high blood pressure have been confirmed, and the importance of correcting hypertension (systemic and glomerular) and proteinuria for slowing disease progression has also been demonstrated. The potential adverse role of a high-protein intake, strongly suggested by experimental studies and the clinical data of uncontrolled trials, has been challenged by the data coming from large controlled trials. The role of lipids needs to be clarified by prospective randomized trials, but the effects of therapeutic interventions aimed at correcting lipid abnormalities seem very promising. The association between the DD genotype of the gene encoding the angiotensin-converting enzyme (ACE) and an increased risk of renal function loss is under evaluation with the aim of identifying the patients who may most benefit from ACE inhibition.