Bisphosphonates have been widely used over the past decade to prevent skeletal complications in breast cancer patients with bone metastases. The skeletal complications associated with bone metastases include severe bone pain, pathologic fractures, spinal cord compression, and hypercalcemia. A number of bisphosphonates, including oral clodronate, intravenous (IV) pamidronate, IV zoledronic acid, and ibandronate have been shown to significantly reduce skeletal complications and palliate bone pain in patients with breast cancer based on placebo-controlled trials. However, only zoledronic acid and pamidronate have been directly compared within a single trial, and zoledronic acid (4 mg via 15- minute infusion) was shown to be significantly more effective than 90 mg pamidronate at reducing the overall risk of skeletal complications in patients with breast cancer. Both IV pamidronate and zoledronic acid are recommended by the American Society of Clinical Oncology for the treatment of malignant bone disease. As we look to the future, the role of bisphosphonates will continue to evolve beyond the prevention of skeletal complications. Encouraging results have recently been reported from studies assessing the effects of bisphosphonates on tumor progression in bone and for the prevention of cancer treatment-induced bone loss.