Kisspeptins are peptides encoded by KISS1. The gene was first discovered in 1996, in Hershey, PA, USA, and was subsequently named after Hershey's chocolate kisses. The peptide product of KISS1 is a 145 aminoacid peptide that is cleaved into four shorter peptides: kisspeptin-54, kisspeptin-14, kisspeptin-13, and kisspeptin-10 (the numbers denote how many aminoacids in each). All these isoforms activate the kisspeptin receptor. Kisspeptins produced in the hypothalamus stimulate neurons in the hypothalamus that secrete gonadotropin-releasing hormone (GnRH), which subsequently stimulates release of gonadotropins and sex steroid hormones. Kisspeptin has been shown to have a crucial role in puberty. Inactivating mutations of the kisspeptin receptor or KISS1 gene lead to pubertal failure due to hypogonadotrophic hypogonadism in mice and in people. Conversely, activating mutations of the kisspeptin receptor in people lead to central precocious puberty. Exogenous kisspeptin stimulates gonadotropin release in all animal species studied and in people. This effect is mediated predominantly by stimulating GnRH release (because pretreatment with a GnRH antagonist completely blocks the ability of kisspeptin to stimulate gonadotropin release). Recent evidence also suggests that the kisspeptin system is important in the generation of GnRH pulses, which are crucial for normal fertility. In a subpopulation of neurons in the hypothalamic arcuate nucleus, kisspeptin colocalises with two other hormones known to affect GnRH release, namely neurokinin B (NKB) and dynorphin (DYN). This group of cells is often referred to as the KNDy neurons. Increasing data suggest that KNDy neurons have a key role in mediation of pulsatile GnRH release. Evidence thus far suggests that kisspeptin has exciting therapeutic potential in people—eg, acute use of kisspeptin for infertility could stimulate reproductive hormone release more naturally than by conventional methods. Data for human beings also suggest that kisspeptin might stimulate pulses of luteinising hormone, indicating its therapeutic potential for the treatment of women with anovulatory infertility. Chronic use of high doses of kisspeptin causes desensitisation and reduces secretion of gonadotropins. Hence, longacting forms of kisspeptin are being developed to treat hormone-sensitive cancers, with promising early results in people.