Bisphosphonates are widely used to stabilize the bone and prevent devastating skeletal complications in patients with malignant bone disease from breast cancer or multiple myeloma. Bisphosphonates work by inhibiting osteoclast-mediated bone resorption and have also demonstrated antitumor activity in preclinical models. Of the available bisphosphonates, intravenous zoledronic acid has demonstrated the broadest clinical activity and is approved for the treatment of bone metastases from any solid tumor in many countries throughout the world. Clinical trials in breast and prostate cancer are also investigating zoledronic acid for the prevention of bone metastasis and bone loss associated with hormonal therapy. Due to its unique pharmacologic profile, zoledronic acid has activity in a variety of clinical settings at low doses and with infrequent intravenous dosing.