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There is a growing body of evidence to show that AGEs, which form and accumulate at an accelerated rate under diabetes and normal aging, are implicated in the pathogenesis of various devastating disorders such as diabetic vascular complications, coronary heart diseases, Alzheimer's disease, cancer growth and metastasis, insulin resistance and nonalcoholic fatty liver disease. In addition, the engagement of the receptor for AGEs, RAGE with the macroprotein derivatives is reported to elicit oxidative stress and vascular inflammation and subsequently activate the downstream signalings, thereby being involved in the development and progression of these devastating disorders. These observations suggest that the AGEs-RAGE axis is a novel therapeutic target for various disorders. In this issue, I would like to reinforce the emerging knowledge regarding AGEs and RAGE as an important mediator in health and disease. I believe that the issue is helpful for most of the researchers and physicians in the field of drug design and clinical pharmacology, especially those who would like to understand the pathophysiological role of the AGEs-RAGE system in health and numerous devastating disorders.