Urinary albumin measurements are currently not standardized due to a lack of a reference method and reference (primary and secondary [matrix]) material. Multiple molecular forms of albumin in urine are identified. Modification of albumin by proteolysis during passage through the urinary tract and chemical modification during specimen storage leads to the formation of albumin fragments. Multiple methods have been developed to quantify albuminuria and significant different results are reported dependent on the available assay. The current point of view of the National Kidney Disease Education Program - IFCC Working Group on Standardization of Albumin considers the immunoassay with polyclonal sera as the primary method of quantifying urine albumin. This article reviews the process of albumin fragmentation and focuses on the controversial topic of immuno-unreactive, nonimmunoreactive, or immunochemically nonreactive albumin fractions and its consequences for albumin analysis. We conclude that at present there are no hard arguments for measuring immunochemically unreactive albumin in urine. Immunoassays using polyclonal antisera for the detection of urinary albumin remain the gold standard. The development of a reference measurement procedure remains one of the challenges for the future.