Determination of human growth hormone (GH) concentration in serum plays a key role in the diagnosis of GH deficiency and GH excess (acromegaly). Methods of measuring GH still lack standardization and show considerable between-method variability. Therefore, correct interpretation of GH test results requires knowledge of measurement techniques and awareness of potential problems in applying recommendations for cut-off values given in the literature. This article focuses on the molecular, structural, and methodologic background of the heterogeneity of assay results and on possible next steps toward standardization.