In recent years compelling evidence has been provided that cell-cell interactions involving non-neuronal cells, such as glial and endothelial cells, are important in regulating the secretion of GnRH, the neuropeptide that controls both sexual development and adult reproductive function. Modification of the anatomical relationship that exist between GnRH nerve endings and glial cell processes in the external zone of the median eminence modulates the access of GnRH nerve terminals to the portal vasculature during the oestrous cycle. The establishment of direct neuro-haemal junctions between GnRH neuroendocrine terminals and the portal vasculature on the day of pro-oestrus may be critical for the transfer of GnRH upon its release into the fenestrated capillaries of the median eminence. Notwithstanding the importance of these plastic rearrangements, glial and endothelial cells also regulate GnRH neuronal function via specific cell-cell signalling molecules. While endothelial cells of the median eminence use nitric oxide to effect this regulatory control, astrocytes employ several growth factors, and in particular those of the EGF family and their erbB receptors to facilitate GnRH release during sexual development. Loss of function of each of these erbB receptors involved in the astroglial control of GnRH secretion leads to delayed sexual development. It is clear that regulation of GnRH secretion by cell-cell communication mechanisms other than transsynaptic inputs is an important component of the central neuroendocrine process controlling mammalian reproduction.