Methylglyoxal (MGO), a byproduct of sugar and lipid metabolic processes, is a major glycating agent. This metabolite reacts with basic residues of proteins and promotes the formation of advanced glycation end products (AGEs). Although MGO and AGEs are widely discussed in the context of diabetes, until recently, MGO was thought to result from insufficient blood sugar control. A new report reveals that plasma MGO, and not blood sugar, distinguishes diabetic patients with no pain from those with pain. This ability brings to MGO a new applicability to disease diagnosis.Diseases with normal sugar conditions, such as hypertension, sepsis, and renal disease, are increasingly recognized as MGO-related. We review the role of MGO in drug-induced nephropathy, induction of hypertension by oral administration, and as a biomarker of sepsis. We also discuss the measurement of MGO and its stable metabolite d-lactate.The metabolism and pathogenic mechanisms of MGO need investigation in diverse disease models. Whether MGO can be considered as an individual pathological factor will be an interesting topic.