Epidemiological studies demonstrate the role of early and intensive glycemic control in the prevention of micro and macrovascular disease in both type 1 and type 2 diabetes mellitus (DM). Hyperglycemia elicits several pathways related to the etiopathogenesis of cardiovascular disease (CVD), including the generation of advanced glycation end products (AGEs). In this review, we revisit the role played by AGEs in CVD based in clinical trials and experimental evidence. Mechanistic aspects concerning the recognition of AGEs by the advanced glycosylation end product-specific receptor (AGER) and its counterpart, the dolichyl-diphosphooligosaccharide-protein glycosyltransferase (DDOST) and soluble AGER are discussed. A special focus is offered to the AGE-elicited pathways that promote cholesterol accumulation in the arterial wall by enhanced oxidative stress, inflammation, endoplasmic reticulum stress and impairment in the reverse cholesterol transport (RCT).