Many pharmacological agents are available for treatment of postmenopausal osteoporosis, including estrogen and the selective modulators of estrogen receptor (SERMS). Bazedoxifene is a third-generation SERM, which acts as estrogen agonist in bone and lipid metabolism and as an antagonist in the breast and endometrium. Studies demonstrated that bazedoxifene reduced significantly the risk of vertebral fractures. In a subgroup of patients at high risk (post-hoc analysis), a reduction of nonvertebral fractures risk was reported. Moreover, the combination of conjugated estrogens with bazedoxifene seems to offer an alternative to classical hormone therapy, improving the vasomotor symptoms and vaginal atrophy, without the use of a progestin. Bazedoxifene is a promising drug for the treatment and prevention of osteoporosis in postmenopausal women; however a safety concern regarding venous thromboembolic events is needed before starting treatment.