The formation of glycohemoglobin, especially the hemoglobin A1c(Hb_(A1c)) fraction, occurs when glucose becomes coupled with the amino acid valine in the β-chain of Hb; this reaction is dependent on the plasma concentration of glucose. Since the early 1970 s it has been known that diabetics display higher values of Hb_(A1c) because they have elevated blood glucose concentrations. Thus Hb_(A1c) has acquired a very important role in the treatment and diagnosis of diabetes mellitus. After the introduction of the first quantitative measurement of Hb_(A1c), numerous methods for glycohemoglobin have been introduced with different assay principles: From a simple minicolumn technique to the very accurate automated highpressure chromatography and lastly to many automated immunochemical or enzymatic assays. In early days, the results of the quality control reports for Hb_(A1c) varied extensively between laboratories, therefore in United States and Canada working groups(WG) of the Diabetes Controls and Complications Trial(DCCT) were set up to standardize the Hb_(A1c) assays against the DCCT/National Glycohemoglobin Standardization Program reference method based on liquid chromatography. In the 1990 s, the International Federation of Clinical Chemistry and Laboratory Medicine(IFCC) appointed a new WG to plan a reference preparation and method for the Hb_(A1c) measurement. When the reference procedureswere established, in 2004 IFCC recommended that all manufacturers for equipment used in Hb_(A1c) assays should calibrate their methods to their proposals. This led to an improvement in the coefficient of variation(CV%) associated with the assay. In this review, we describe the glycation of Hb, methods, standardization of the Hb_(A1c) assays, analytical problems, problems with the units in which Hb_(A1c) values are expressed, reference values, quality control aspects, target requirements for Hb_(A1c), and the relationship of the plasma glucose values to Hb_(A1c) concentrations. We also note that the acceptance of the mmol/mol system for Hb_(A1c) as recommended by IFCC, i.e., the new unit and reference ranges, are becoming only slowly accepted outside of Europe where it seems that expressing Hb_(A1c) values either only in per cent units or with parallel reporting of percent and mmol/mol will continue. We believe that these issues should be resolved in the future and that it would avoid confusion if mmol/mol unit for Hb_(A1c) were to gain worldwide acceptance. The formation of glycohemoglobin, especially the hemoglobin A1c (Hb_ (A1c)) fraction, occurs when glucose becomes coupled with the amino acid valine in the β-chain of Hb; this reaction is dependent on the plasma concentration of glucose. Since the early 1970 s it has has been known that diabetics display higher values ​​of Hb_ (A1c) because they have elevated blood glucose concentrations. Thus Hb_ (A1c) has acquired a very important role in the treatment and diagnosis of diabetes mellitus. Numerous methods for glycohemoglobin have been introduced with different assay principles: From a simple minicolumn technique to the very accurate automated high pressureure chromatography and lastly to many automated immunochemical or enzymatic assays. In early days, the results of the quality control reports for Hb_ (A1c) varied extensively between laboratories, therefore in United States and Canada working groups (WG) of the Diabetes Contr ols and Complications Trial (DCCT) were set up to standardize the Hb_ (A1c) assays against the DCCT / National Glycohemoglobin Standardization Program reference method based on liquid chromatography. In the 1990 s, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) appointed a new WG to plan a reference preparation and method for the Hb_ (A1c) assays. When the reference procedures established, in 2004 IFCC recommended that all manufacturers for equipment used in Hb_ (A1c) assays should calibrate their methods to their proposals. In this review, we describe the glycation of Hb, methods, standardization of the Hb_ (A1c) assays, analytical problems, problems with the units in which Hb_ (A1c) values ​​are expressed, reference values, quality control aspects, target requirements for Hb_ (A1c), and the relationship of the plasma glucose values ​​to Hb_ (A1c) concentrations. We also note that the acceptance of the mmol / mol system for Hb_ (A1c) as recommended by IFCC, ie, the new unit and reference ranges, are becoming only accepted by Europe where it seems that expressing Hb_ (A1c) values ​​either only We believe that these issues should be resolved in the future and that it would avoid confusion if mmol / mol unit for Hb_ (A1c) were to gain worldwide acceptance.