Evidence has been accumulated that sex hormone-binding globulin (SHBG) does not act only as a regulator of bioavailability of sex steroids, but represents an important factor in various endocrine regulatory systems. As documented by both clinical and in vitro studies, SHBG biosynthesis in the liver and also in other tissues is under the control of various hormones and other regulatory factors as estrogens, thyroid hormones, insulin, growth hormone and insulin-like growth factor-I (IGF-I). In addition to its effect on transport and uptake of sex hormones by their target cells, SHBG may act as a true hormone through its membrane receptors of the latter targets. The recent data on the over-all role of SHBG in endocrine regulations are critically reviewed here.