The vagina provides a local and a systemic route for delivering hormones for systemic effects and uterine targeting. Due to the 'uterine first-pass effect', hormones concentrate in the uterus and nearby tissues with low systemic exposure. Vaginal oestrogens, progesterone/progestins and danazol are currently used to obtain local (vagina and urethra), regional (uterus, pelvic structures) and systemic effects or contraception. Very low dosages of transvaginal oestrogens in the forms of creams, tablets and rings are effective for vaginal atrophy and urinary incontinence. To avoid endometrial stimulation, no deep vaginal application of low dosages for less than 6 months is recommended. For postmenopausal hormonal therapy by the vaginal route, progesterone is delivered directly to the uterus; the target organ for which it is designed. Worldwide, vaginal progesterone is employed for luteal phase support. Contraceptive vaginal rings offer the advantages of non-oral administration and sustained release. Vaginal administration of steroids is a promising option for the treatment of endometriosis.