Diabetic complications are a leading cause of blindness, renal failure, and nerve damage. Additionally, diabetes-accelerated atherosclerosis leads to increased risk of myocardial infarction, stroke, and limb amputation. At the present time, 4 main molecular mechanisms have been implicated in hyperglyceamia-mediated vascular damage. In particular, advanced glycation endproducts (AGE), which are formed by complex, heterogeneous, sugar-derived protein modifications, have been implicated as a major pathogenic process for diabetic complications. Recently, AGE inhibitors such as aminoguanidin, ALT-946, and pyridoxamine have been reported. Such an integrating paradigm provides a new conceptual framework for future research on diabetes complications and on discovering drugs to prevent the progression of AGE-induced maladies.