The roles of initially kisspeptin and subsequently neurokinin B pathways in the regu-lation of human reproduction through the control of GnRH secretion were first iden-tified 20 years ago, as essential for the onset of puberty in both boys and girls.Within that short time we already now have the first licence for clinical use for a neu-rokinin antagonist in a related indication, for menopausal vasomotor symptoms.Between these two markers of the start and end of the reproductive lifespan, it isclear that these pathways underlie many of the aspects of the hypothalamic regula-tion of reproduction which had hitherto been enigmatic. In this review, we describethe data currently available from studies designed to elucidate the roles of kisspeptinand neurokinin B in human ovarian function, specifically the regulation of follicledevelopment leading up to ovulation, and in the control of the mid-cycle GnRH/LHsurge that triggers ovulation. These studies, undertaken with only very limited phar-macological tools, provide evidence that the neurokinin B pathway is important incontrolling the hypothalamic contribution to the precise gonadotropic drive to theovary that is necessary for mono-ovulation, whereas the switch from negative topositive estrogenic feedback results in kisspeptin-mediated increased GnRH secre-tion. Potential therapeutic opportunities in conditions characterised by disorderedhypothalamic/pituitary function, polycystic ovary syndrome, and functional hypotha-lamic amenorrhoea, and in the induced LH surge that is a necessary part of IVF treat-ment are discussed
