The kisspeptin/kisspeptin receptor (KISS1R) system is a critical regulator of reproductive function. The kisspeptins are potent stimulators of the hypothalamic-pituitary-gonadal (HPG) axis via their actions ongonadotropin-releasing hormone. Therefore, kisspeptins represent putative drug targets for the treatment of reproductive diseases. Kisspeptins of 10, 13, 14 and 54 amino acids in length have been identified, all of which contain a C-terminal decapeptide that is essential for biological activity. The longest form, kisspeptin-54, may be the most bioactive in vivo. Moreover, the pattern of kisspeptin administration is important; whereas single or intermittent injections of kisspeptin generally stimulate the HPG axis, continuous administration leads to the desensitization of the HPG axis to the effects of the peptide. Several kisspeptin analogs have been developed, and are discussed in relation to their activity at the KISS1R and to their in vivo HPG axis effects.