Central precocious puberty (CPP) results from premature activation of hypothalamic-pituitary-gonadal axis, with the consequent increase of gonadotropin-releasing hormone (GnRH); GnRH agonists (GnRHa) represent the gold-standard therapy in children with CPP although their use might be responsible for pituitary GnRH receptors down-regulation, that in turn suppresses luteinizing hormone (LH) and follicle stimulating hormone (FSH) and blocks of gonadal sex hormones release. This evidence concerns the gene GNRH1 and precocious puberty.