A large body of evidence has implicated reactive carbonyl compounds as glycotoxic mediators of carbonyl stress. This review is focused on the pathophysiological effects of α-oxoaldehydes in diabetes and related complications, summarizing the state-of-the-art on the endogenously produced carbonyls methylglyoxal, glyoxal and 3-deoxyglucosone, formed as glycolytic intermediates during metabolic conversion of glucose, via Maillard reaction by degradation of glycated proteins, and during lipid peroxidation process. Their role in the advanced glycation process and detrimental effects on vascular tissue are discussed.