The natural gonadotropin-releasing hormone (GnRH) is secreted by hypothalamic neurons and acts at the level of anterior pituitary gonadotrophs releasing the peptides luteinizing hormone and follicle-stimulating hormone. GnRH is a decapeptide sensitive to peptidases, resulting in a short half-life. The synthesis of highly potent analogues of GnRH provides peptides with a longer half-life and a higher affinity to the GnRH-receptor. The presently available GnRH analogues for clinical use act initially as agonists by upregulating GnRH receptors in the pituitary. A few days after continuous application of GnRH analogues down-regulation of receptors and desensitization of the pituitary occur. In addition to receptor mechanisms, a number of postreceptor actions at the level of second messengers (protein kinase C, leukotriene and inositol phosphates) are responsible for the inhibition of adequate gonadotropin secretion. This paradoxical entire fertility action of the analogues is the basic principle for its clinical use, resulting in a reversible suppression of pituitary and thereby ovarian function.