Growth hormone (GH) is synthesized and released by somatotrophic cells in the pituitary gland. As well as functions in growth and development, GH is also important in many metabolic diseases. The biological functions of GH are initiated by ligand binding to the surface receptor,growth hormone receptor (GHR). Rapid advances in molecular technology have enabled construction of various GHR knockout mice models to examine the mechanisms of action of GH. Using a Cre ?LoxP recombinase system, the mouse GHR has also been successfully knocked out systemically and tissue?specifically, including in the liver, skeletal muscle, adipose tissues, macrophages, and pancreatic islet β?cells. This has provided a unique platform for studying GH/ GHR signal transduction and its interactions with other signaling pathways. In this brief review, we discuss the phenotypic characteristics and applications of these GHR knockout mouse models.