Treatment of growth hormone (GH) deficiency via parenteral administration of recombinant hGH has greatly benefited from recombinant DNA technology allowing production of practically unlimited amounts of the pure hormone. However, an alternative approach that may lead to correction of the clinical defect is presented by hGH gene transfer into somatic cells of the patient, either ex vivo or in vivo. This approach has not only the potential advantage of circumventing repetitive injections of the hormone and its laborious isolation and purification processes, but can also, in principle, provide a mechanism of hormone delivery that resembles the natural process. GH gene therapy has not reached the clinics yet, but several interesting and promising animal models for this treatment have been developed and studied. They are not only potentially useful for elucidation of the still unresolved mechanism of sustained in vivo gene product delivery, but also for opening the way to therapy of other protein deficiencies for which gene therapy may be the only viable option. This review article describes, analyzes and compares the major animal models of GH gene therapy that have been developed in the last two decades.