Early renal insufficiency (ERI), defined as a calculated or measured glomerular filtration rate (GFR) between 30 and 60 mL/min per 1.73 m2, is present in more than 10% of the adult Australian population. This pernicious condition is frequently unrecognised, progressive and accompanied by multiple associated comorbidities, including hypertension, renal osteodystrophy, anaemia, sleep apnoea, cardiovascular disease, hyperparathyroidism and malnutrition. Several treatments have been suggested to retard GFR decline in ERI, including blood pressure reduction, angiotensin-converting enzyme inhibition, angiotensin receptor antagonism, calcium channel blockade, cholesterol reduction, smoking cessation, erythropoietin therapy, dietary protein restriction, intensive glycaemic control and early intensive multidisciplinary patient education within a renal unit. In addition, specific interventions have been reported to be renoprotective in atherosclerotic renal artery stenosis, diabetic nephropathy, lupus nephritis and certain forms of primary glomerulonephritis. The present paper reviews the available published randomised controlled clinical trials and meta-analyses supporting (or refuting) a role for each of these therapeutic manoeuvres.