One in six couples will face infertility. Excessively high prolactin in the blood is a major cause of infertility in both males and females. The mechanism by which prolactin affects fertility is not fully understood, but it involves an inhibitory action on the hypothalamic neurons controlling reproduction (GnRH neurons). We have shown that GnRH neurons do not have prolactin receptors, hence prolactin must be indirectly regulating these neurons through other prolactin-sensitive pathways. We have recently identified that kisspeptin neurons, a key neuronal pathway regulating GnRH neurons, express prolactin receptors. Using state-of-the art transgenic approaches that are unique to our laboratory, we are in a position to critically test the hypothesis that prolactin regulation of kisspeptin neurons is required for infertility induced by hyperprolactinemia. These studies will help develop better treatments for infertility, and may provide opportunity for the development of novel contraceptives.