The central functions of kisspeptin and the kisspeptin receptor (KISS1R) in regulating mammalian reproductive development and fertility were unnoticed until 2003, when three groups independently reported the presence of deletion and inactivating mutations of KISS1R in humans (Seminara et al., 2003; De Roux et al., 2003) and mice (Seminara et al., 2003; Funes et al., 2003) suffering from hypogonadotropic hypogonadism; a syndrome characterized by delayed or absent pubertal development secondary to gonadotropin deficiency. This evidence concerns the gene KISS1R and hypogonadotropic hypogonadism.