The Kiss-1 gene encodes a secreted protein that is proteolytically cleaved to produce a number of structurally related peptides, with high interspecies conservation, globally termed kisspeptins. The original niche for the role of kisspeptin in human physiology is derived from cancer biology, with the loss of Kiss-1 expression being associated with poor prognosis in several malignancies. However, kisspeptin has recently emerged as a fundamental player in the field of reproductive biology. Genetic analysis of large consanguineous pedigrees by two independent groups led to the association of inactivating mutations of GPR54, the receptor which mediates kisspeptin action, with idiopathic hypogonadotropic hypogonadism. In the present paper the most salient aspects of the multifaceted role of kisspeptin in the reproductive system are reviewed, including the association of kisspeptin with the gonadal steroid feedback loop and the triggering of puberty onset.