The secretion of growth hormone (GH) is controlled by a complex regulatory system. The primary control is exerted by two neuroendocrine hormones, GH-releasing hormone and somatostatin, though other hypothalamic neuropeptides directly and indirectly participate in this process. The regulation of each of these neurohormones is now being clarified at both physiologic and molecular levels, as are their respective roles in the generation of pulsatile GH secretion and in GH feedback regulation. Considerable information has been amassed concerning signal transduction systems mediating the effects of hypothalamic hormones on GH secretion. Although multiple second messengers have been implicated, the adenylate cyclase-cyclic AMP-protein kinase A system appears to exert a predominant role. The developmental regulation of the somatotropes and of GH gene expression is also of importance in determining the GH responses to releasing and inhibiting hormones. The availability of several rodent strains with genetic disorders of growth associated with impaired GH secretion, along with the development of transgenic models, has permitted a more detailed analysis of the role of cytokines and growth factors on both somatotrope biology and hormone secretion. Finally, knowledge gained from studies in animals is permitting a better understanding of the mechanisms involved in physiologic GH secretion and altered GH secretion associated with specific disease states in humans.