Nephropathy is a common microvascular complication among patients with type 2 diabetes mellitus and a major cause of kidney failure. It is characterized by albuminuria (≥ 300 mg/d) and a reduced glomerular filtration rate and is often present at the time of diabetes diagnosis after the kidney has been exposed to chronic hyperglycemia during the prediabetic phase. A low glomerular filtration rate (<60 mL/min/1.73 m(2)) is also an independent risk factor for cardiovascular events and death. Detection of diabetic nephropathy during its initial stages provides the opportunity for early therapeutic interventions to prevent or delay the onset of complications and improve outcomes. An intensive and multifactorial management approach is needed that targets all risk determinants simultaneously. The strategy should comprise lifestyle modifications (smoking cessation, weight loss, increased physical activity, and dietary changes) coupled with therapeutic achievement of blood glucose, blood pressure, and lipid goals that are evidence-based. Prescribing decisions should take into account demographic factors, level of kidney impairment, adverse effects, risk of hypoglycemia, tolerability, and effects on other risk factors and comorbidities. Regular and comprehensive follow-up assessments with appropriate adjustment of the therapeutic regimen to maintain risk factor control is a vital component of care, including referral to specialists, when required.