The discovery of the kisspeptin (Kp) system stirred a burst of research in the field of reproductive neuroendocrinology. In the last 15 yr, the organization and activity of the system, including its neuroanatomical structure, its major physiological functions, and its main pharmacological properties, were outlined. To this endeavor, the use of genetic tools to delete and to restore Kp system functionality in a specific tissue was essential. At present, there is no question as to the key role of the Kp system in mammalian reproduction. However, easily applicable genetic manipulations are unavailable for domestic animals. Hence, many essential details on the physiological mechanisms underlying its action on domestic animals require further investigation. The potentially different effects of the various Kp isoforms, the precise anatomical localization of the Kp receptor, and the respective role played by the 2 main populations of Kp cells in different species are only few of the questions that remain unanswered and that will be illustrated in this review. Furthermore, the application of synthetic pharmacologic tools to manipulate the Kp system is still in its infancy but has produced some interesting results, suggesting the possibility of developing new methods to manage reproduction in domestic animals. In spite of a decade and a half of intense research effort, much work is still required to achieve a comprehensive understanding of the influence of the Kp system on reproduction. Furthermore, Kp system ramifications in other physiological functions are emerging and open new research perspectives.