A significant proportion of total circulating growth hormone (GH) is bound to a high affinity growth hormone binding protein (GHBP). Several low affinity binding proteins have also been described. Significant differences between species exist with respect to origin and regulation of GHBP, but generally it resembles the extracellular domain of the GH receptor. Concentrations are associated with GH status, body composition and other factors. Although the clinical relevance of GHBP is not fully understood it is suggested that concentrations indirectly reflect GH receptor status. This is supported by cases of Laron's syndrome where a molecular defect in the extracellular domain of the GH receptor is associated with low or unmeasurable GHBP concentrations. Methods to measure GHBP have evolved from chromatographic, activity based procedures to direct immunoassays. In clinical practice, measurement of GHBP can be helpful to differentiate between GH deficiency and GH insensitivity, particularly if GHBP is absent.