Measurement of circulating growth hormone (GH) concentrations is essential in diagnosis of either GH deficiency or GH excess. The invention of immunoassays for the measurement of peptide hormones was a major breakthrough, enabling the routine analysis of GH concentrations in larger series of samples. Over the last few decades, measurement technology has evolved from less sensitive, mainly radioactive assays based on polyclonal antisera to the latest generations of highly sensitive chemiluminescence methods employing monoclonal antibodies. Unfortunately, the development of newer assays did not lead to better agreement among the results obtained by different assay methods. On the contrary, the differences tended to increase when monoclonal antibody based assays became more popular. The actual value reported for the GH concentration in a specific patient's sample still mainly depends on the method used by the respective laboratory, limiting the applicability of international consensus guidelines in clinical practice. The heterogeneity of the analyte itself, the availability of different reference preparations for calibration and the interference from matrix components such as GH binding protein are among the reasons why standardizing GH assays is difficult. An additional challenge arose from the availability of a GH receptor antagonist for the treatment of acromegaly, which is basically a mutated form of GH and therefore interferes in many GH assays. This review provides an overview on GH assays used in clinical practice, their limitations and the potential next steps towards standardization.