Recent clinical studies have substantiated the concept of 'metabolic memory' in the pathogenesis of cardiovascular disease (CVD) in diabetes. Indeed, DCCT-EDIC Research, has revealed that intensive therapy during the DCCT reduces the risk of cardiovascular events by about 50% in type 1 diabetic patients 11 years after the end of the trial. Among various biochemical pathways activated under diabetic conditions, the process of formation and accumulation of advanced glycation end products (AGEs) and their mode of action are most compatible with the theory of 'metabolic memory'. Further, there is a growing body of evidence that AGEs and their receptor RAGE interaction plays an important role in CVD in diabetes. These observations suggest that the blockade of AGE-RAGE system may be a promising therapeutic target for CVD in diabetes. In this paper, we review the role of the AGE-RAGE axis in diabetic macroangiopathy.