According to the latest IDF Diabetes Atlas, diabetes mellitus (DM) caused an estimated 5.1 million deaths worldwide in 2013. In other words, a person died from this epidemic disease every six seconds. DM has become one of three major causes of human death after cardiovascular disease and cancers. Glycated human hemoglobin HbA_1c is generated by the irreversible, non-enzymatic glycation reactions on the α-amino groups of N-terminal residue Val1 in one or both beta subunits of tetrameric Hb. Due to the direct correlation of HbA_1c with ambient glycemic concentration over a prolonged period of time, HbA_1c could be useful in assessing diabetic control for the long-term, and is also an important predictor of potential risks to diabetes complications. Therefore, ADA and WHO recommended HbA_1c with a diagnostic cut point of ≥ 6.5% as a new diagnostic criterion for diabetes in 2010 and 2011, respectively. In this review, we summarize: (1) the standardization of HbA_1c from the global IFCC reference method and designated comparison methods in the United States, Japan and Sweden; (2) the basic principles of HbA_1c detection methods commonly used in clinic including affinity chromatography, immunoassay and enzymatic analysis, and their application limitations; (3) the development of POC technology for HbA_1c measurement.