This paper focuses on the question whether different estrogens (E) have different qualitative pharmacodynamic effects when used by women for contraception, Hormone Replacement Therapy (HRT) or prevention of osteoporosis. In this context estrogens have been defined as the estrogen agonists estradiol (E2), estrone (E1), estriol (E3), conjugated equine estrogens (CEE), diethylstilbestrol (DES) and ethinylestradiol (EE). Selective Estrogen Receptor Modulator's (SERM's) have been excluded from this analysis primarily because of lack of comparative (clinical) data with estrogen agonists. A major problem when addressing the issue of comparability of estrogen agonists is the lack of data from head-to-head estrogen-only comparative studies. Comparative studies have been performed almost exclusively with estrogen agonists combined with a series of different progestogens (P), that have been added to protect the uterus from endometrial hyperplasia. Since progestogens are known to exhibit different intrinsic pharmacodynamic properties and interactions with estrogens, it is impossible to judge which role the estrogen plays when qualitative differences between different combined E/P preparations are observed. In summary, no convincing evidence has been found that the estrogens mentioned differ qualitatively. Obviously quantitative differences are present due to differences in e.g. receptor affinity, metabolism (half life) and route of administration (transdermal/vaginal). Since DES has been discarded for human use due to teratogenicity, EE used in all combined E/P oral contraceptives is the most potent estrogen agonist available at present. In HRT, E2 and CEE are equally effective for the treatment of hot flushes and urogenital atrophy and superior to any other treatment option. For long term treatment to prevent osteoporosis and even for short term HRT, estrogen agonists are heavily debated recently because of a small increased risk of breast cancer, that has been known for a long time already. Well informed and individualised choice of treatment seems the appropriate solution.