The prevalence and severity of periodontal disease is increased in patients with both insulin-deficient and insulin-resistant forms of diabetes. While a number of underlying factors likely contribute to enhanced periodontal inflammation and alveolar bone loss in diabetes, a common characteristic of these disorders, regardless of etiology, is the presence of hyperglycemia. A critical consequence of hyperglycemia is non-enzymatic glycation and oxidation of proteins and lipids. After a series of reversible reactions which lead to the generation of Schiff bases/Amadori products, a further series of complex molecular rearrangements ensues which results in the formation of the irreversible advanced glycation end products, or AGEs. AGEs accumulate during the process of normal aging in the plasma and tissues, but to an accelerated degree in patients with diabetes. A central means by which AGEs are believed to impart their pathogenic effects is via interaction with specific cellular receptors; the best-characterized of these is receptor for AGE, or RAGE. RAGE, a member of the immunoglobulin superfamily of cell surface molecules, is present in increased levels on target cells in diabetes, such as endothelial cells and monocytes. One consequence of AGE-RAGE interaction is the generation of enhanced cellular oxidant stress, a means by which cell signaling pathways may be activated, thereby resulting in altered cellular phenotype and cellular dysfunction. In this report, we will review our studies to date on AGEs and RAGE and consider the implications of their enhanced interaction in the pathogenesis of accelerated periodontal disease in diabetes.