Glycated hemoglobin is measured as HbA1c and is the result of an irreversible non-enzymatic glycation of the beta chain of hemoglobin A. HbA1c is used routinely to assess long term glycemic control in patients with diabetes mellitus. There are more than 20 determination methods, the techniques used are cation-exchange chromatography, electrophoresis, affinity chromatography and immunoassays, although each of these techniques measures a different fraction of the glycated hemoglobin. In addition, genetic hemoglobin variants and chemically modified derivates of hemoglobin can affect the HbA1c measurement and thus can not be included in international attempts for standardization. This manuscript reviews the current information on glycation of hemoglobin, HbA1c determination methods, interferences and attempts for standardization. We aim at pointing out to the reader the current problems of glycated hemoglobin determination and to describe the necessary measures which need to be taken for proper measurement of HbA1c.