Menopause occurs on average at age 51.4 years. Most, but not all, women who undergo menopause experience significant vasomotor symptoms (VMS). Although single agent estrogen therapy can relieve VMS, over time estrogen can stimulate the endometrial lining leading to an increased risk for endometrial hyperplasia and adenocarcinoma. Although a progestin has traditionally been given in combination with estrogen to 'protect' the endometrium, a new and innovative approach to this traditional combination hormone therapy is to substitute the progestin with an alternative agent. One such alternative agent is bazedoxifene, an estrogen agonist-antagonist. Based on data from randomized trials, when bazedoxifene is given in combination with oral conjugated estrogens to post-menopausal women, the risk of estrogen-associated endometrial stimulation is significantly reduced. The combination of bazedoxifene and conjugated estrogens has also been shown to relieve menopause-associated VMS and vaginal atrophy, and has been shown to be safe for short-term use. Long-term studies of this combination are needed to determine if the combination of conjugated estrogens/bazedoxifene can be used for >3 years without increasing the risk of breast cancer, stroke, cognitive deficit, pulmonary embolism or coronary heart disease. Short-term data regarding this combination has been submitted to the FDA and is currently under review for clinical use, with the relief of VMS as its primary indication. Data regarding the effects of combination conjugated estrogens/bazedoxifene therapy on bone are promising in terms of the prevention and treatment of post-menopausal osteoporosis.