Estrogen replacement therapy (ERT) has demonstrated significant, long-term benefits by improving cardiovascular risk factors and increasing bone mineral density; however, unopposed ERT is associated with an increased incidence of endometrial hyperplasia and progression to endometrial carcinoma in postmenopausal women who retain their uteri. As a result, the use of combined regimens containing both a progestogen and an estrogen is becoming the standard course of therapy. Further study is required, however, to determine the effects of the various available progestogens and discover optimal dosing regimens. Not all progestogens are alike. Careful progestogen selection is critical to ensure a high degree of patient adherence to therapy. Patients discontinue hormone replacement therapy (HRT) for reasons including irregular or breakthrough bleeding, progestogen intolerance and other unpleasant side effects. Working individually with patients to optimize HRT regimens is critical to helping them continue to use HRT long enough to achieve the long-term benefits.