Standard pharmacological antiresorptive therapy for the prevention and/or treatment of postmenopausal osteoporosis now consists of four categories of drugs: estrogens, a selective estrogen receptor modulator (SERM), bisphosponates, and calcitonin. All of these drugs have been studied in randomized controlled trials, but meaningful comparisons of the efficacy of drugs have been difficult due to differences in baseline risks for fracture and differences in study design, including calcium and vitamin D supplementation, definition of fracture, and discontinuation rates. The current paper reviews results from pivotal studies of antiresorptive therapies with fracture as a primary endpoint, as well as head-to-head trials comparing these therapies using surrogate markers of fracture risk, and introduces the first head-to-head trial with fracture as a primary endpoint. The Evista Alendronate Comparison (EVA) trial, a multi-center, double-blind, double-dummy, randomized trial with two active treatment arms is currently underway to compare directly the osteoporotic fracture risk reduction efficacy of raloxifene and alendronate in postmenopausal women with osteoporosis as defined by bone mineral density. The results from this trial will permit more informed judgment by practitioners and provider groups concerning the relative clinical utility of these two drugs.