The access of reproductive steroids to their target cells varies considerably between tissues, and is influenced to a great extent by their interactions with plasma steroid-binding proteins, and with SHBG and CBG in particular. An increased awareness of how SHBG and CBG function within the blood circulation, and within extravascular compartments of steroid-responsive target tissues, needs to be incorporated into the design and evaluation of therapies involving the administration of both natural and synthetic steroids, which influence female reproduction and healthy aging.