Vascular complications result in disabilities and short life expectancy in diabetic patients. During prolonged hyperglycemic exposure, non-enzymatically glycated protein derivatives termed advanced glycation endproducts (AGE) are formed at an accelerated rate and accumulated in blood and in tissues. Studies performed in vitro and in vivo revealed AGE and their receptor RAGE as the major accounts for vascular cell derangement characteristic of diabetes. The AGE-RAGE system would thus be considered as a candidate molecular target for overcoming diabetic vascular complications. Potential preventive and therapeutic approaches toward it include inhibition of AGE formation, breakage of preformed AGE-proteins crosslinks, blockade of AGE-RAGE interactions with RAGE competitors or antagonists and RAGE-specific signaling inhibition.