Metastatic bone disease puts an enormous burden on patients and health care resources. Disruption of normal bone homeostasis by bone metastases leads to troublesome skeletal complications, such as bone pain, pathologic fractures, hypercalcemia of malignancy, and spinal cord compression. Bisphosphonates are an effective treatment for skeletal complications. These agents act primarily by initiating biochemical processes that ultimately result in apoptosis of osteoclasts, but they also have a number of other antitumor functions (eg, inhibition of angiogenesis). At present, the most widely used bisphosphonates are oral clodronate and intravenous pamidronate and zoledronic acid. Although these agents are effective in reducing skeletal complications, they are associated with varying safety and convenience issues. More recently, the availability of ibandronate as intravenous and oral formulations represents a new alternative for the treatment of metastatic bone disease. Further studies are necessary to establish the comparative benefits of bisphosphonates in metastatic bone disease.