The hypothalamo-pituitary-gonadal hormone axis is centrally controlled by a complex regulatory network of excitatory and inhibitory signals, that is dormant during infantile and juvenile periods and activated at puberty. The kisspeptins are the peptide products of the KiSS-1 gene and the endogenous agonists for the G protein-coupled receptor 54(GPR54). Although KiSS-1 was initially discovered as a metastasis suppressor gene, a recent evidence suggests the KiSS-1/GPR54 system is a key regulator of the reproductive system. Yet the actual role of the KiSS-1/GPR54 system in the neuroendocrine control of gonadotropin secretion remains largely unexplored, the system could be the first missing link in the reproductive hormonal axis. Central or peripheral administration of kisspeptin stimulates the hypothalamic-pituitary-gonadal axis, increasing circulating gonadotropin levels in rodents, sheep, monkey and human models. These effects appear likely to be mediated via the hypothalamic GnRH neuron system, although kisspeptins may have direct effects on the anterior pituitary gland. The loss of function mutations of the GPR54(GPR54-/-) have been associated with lack of puberty onset and idiopathic hypogonadotropic hypogonadism(IHH). So kisspeptin infusion may provide a novel mechanism for HPG axis manipulation in disorders of the reproductive system.