This article reviews lasofoxifene, a new-generation selective estrogen receptor modulator (SERM) that is currently in Phase III development for the prevention and treatment of osteoporosis in postmenopausal women. This compound selectively binds to both of the estrogen receptors with a high affinity and a median inhibitory concentration that is similar to that seen with estradiol and > or = 10-fold higher than those reported for other SERMs (raloxifene and tamoxifen). Lasofoxifene has a remarkably improved oral bioavailability with respect to other SERMs due to increased resistance to intestinal wall glucuronidation. In both preclinical and short-term studies, the compound showed a favourable safety profile and demonstrated a proven efficacy in preventing bone loss and lowering cholesterol levels. Dose modelling from Phase II studies allowed the selection of lasofoxifene 0.25 mg/day as the lowest fully effective dose.