Uterine leiomyomas are the most frequent benign disease of the female reproductive tract. To date, the standard treatment of uterine leiomyomas is laparotomic/laparoscopic excision in women who want to preserve their fertility, whereas the use of a more extensive surgery, such as hysterectomy, is reserved for disseminated uterine leiomyomatosis, usually in the perimenopausal period. Given the pathogenesis of uterine leiomyomas, it is clear that future treatments for leiomyomas may be medical. At present the only clinically relevant medical treatment of uterine leiomyoma is GnRH agonist administration in depot formulations. In this review, the use of GnRH agonists, with or without “add-back therapy,” and antagonists will be assessed.