Unlike assays for ions and small molecules protein and peptide measurements depend entirely on comparison of a test sample with a calibrator. Owing to the innate molecular heterogeneity of proteins it is frequently impossible to ensure that the calibrator is identical to the test and this may give rise to dissimilar behaviour in assays. Despite these fundamental limitations it is clear that internationally agreed calibrators are essential and properly used greatly improve homogeneity of reporting of protein values in biological fluids. Unfortunately, only international units can be ascribed to these materials with confidence and the use of mass values which are not internationally agreed has jeopardized the value of international calibrants.