Diabetes is associated with a greatly increased risk of cardiovascular disease (CVD), which cannot be explained only by known risk factors, such as smoking, hypertension, and atherogenic dyslipidemia, so other factors, such as advanced glycation end-products (AGEs) and oxidative stress, may be involved. In this frame, hyperglycemia and an increased oxidative stress (AGE formation, increased polyol and hexosamine pathway flux, and protein kinase C activation) lead to tissue damage, thus contributing to the onset of cardiovascular complications. Several studies have identified in various cell systems, such as monocytes/macrophages and endothelial cells, specific cellular receptors (RAGE) that bind AGE proteins. The binding of AGEs on RAGE induces the production of cytokines and intracellular oxidative stress, thus leading to vascular damage. Soluble RAGE levels have been identified as hypothetical markers of CVD, but, in this regard, there are sparse and conflicting data in the literature. The purpose of this review was to examine all the available information on this issue with a view to clarifying or at least highlighting the points that are still weak, especially from the point of clinical view.