Diabetes and hypertension are major contributors to the increasing incidence of progressive renal disease. In addition to more potent antihypertensive agents that block the renin-angiotensin system, drugs that modulate other pathogenetic pathways are also in development. Recent preclinical studies indicate that compounds that interfere with the formation and action of advanced glycation end products may have a role in the treatment and prevention of diabetic nephropathy, as may agents targeting the activity of protein kinase C.