Several medications are effective in reducing the incidence of osteoporotic fractures. Vertebral and nonvertebral fractures can be reduced by 30-65% by administering anticatabolic agents (e.g. raloxifene, alendronate, and risedronate) or anabolic agents (e.g. the active parathyroid hormone fragment teriparatide and strontium ranelate). These medications were investigated in placebo-controlled randomized trials in vast populations. Study extensions provided information on long-term efficacy and safety. However, the best strategy for using these medications in high-risk individuals remains unclear. For instance, the relative merits of starting with an anabolic agent or on an anticatabolic agent have not been compared. The patient's age, severity of the osteoporosis (bone mineral density and risk factor profile), specific characteristics of each medication, and patient preferences regarding drug-dosing modalities should be considered. Compliance must be evaluated regularly. Whereas minimal treatment durations have been determined, optimal durations remain incompletely evaluated and should be determined on a case-by-case basis according to the severity of the bone disease and to the treatment response in terms of clinical features and bone mineral density. Synchronous and t treatment combinations have been evaluated. Disappointing results were obtained with synchronous parathyroid hormone and bisphosphonate therapy. In contrast, the parathyroid hormone-bisphosphonate sequence holds promise for the treatment of severe postmenopausal osteoporosis with at least two vertebral fractures. However, little is known about potential synergies among medications in terms of fracture risk reduction. Synchronous and sequential regimens have not been compared in randomized clinical trials, and such trials would be extraordinarily difficult to design. Nevertheless, available data allow a number of suggestions regarding treatment strategies. The most important step is deciding to start effective treatment (raloxifene, bisphosphonate, teriparatide, or strontium ranelate) in patients at risk for fractures. Patients should be given detailed information on potential benefits and long-term treatment modalities.