The cancer patient with skeletal metastases now has a much improved range of treatment options with major advances in bone-specific drug therapy as well as radiotherapy and radiopharmaceuticals, orthopaedic surgery, and systemic anticancer therapy with cytotoxic and endocrine agents. Recent advances in the understanding of bone remodeling mechanisms and the interdependence of cancer cells and bone have been closely associated with development of the bisphosphonate drugs and newer agents such as osteoprotegerin (OPG). The bisphosphonates are potent inhibitors of osteoclast mediated bone resorption and appear to function either by induction of apoptosis in mature osteoclasts or by inhibition of formation of osteoclasts from progenitor cells. Bisphosphonates are the treatment of choice in tumor-induced hypercalcemia. Bisphosphonates have a clear role in reducing bone pain and skeletal complications, such as pathological fracture and are being evaluated in the prevention of bone metastases. Until recently, intravenous (IV) pamidronate has been the drug most commonly prescribed for oncological indications and oral clodronate has also been widely used in some countries outside the US. However, newer and more potent drugs, such as zoledronate, are increasingly having a major impact on routine therapy. Three of the largest ever bisphosphonate trials, using zoledronate in metastatic bone disease have recently been completed. In a breast and multiple myeloma trial in 1648 patients, zoledronate (4mg IV) was shown to be equivalent to pamidronate (90mg IV) in reducing skeletal events and was more convenient to administer. In trials in prostate cancer and a wide range of other solid tumor types affecting bone, both the number of patients with skeletal-related events and the rate of bone complications were reduced. The indications for bisphosphonates are, therefore, no longer constrained by tumor type. The assessment of response to therapy is a vital part of management of metastatic bone disease. Plain radiographs and the isotope bone scan remain widely used but have many limitations. Newer imaging techniques such as computerized tomography, magnetic resonance imaging, and positron emission tomography may be useful in selected situations. Recent research suggests that measurement of tumor markers and bone-specific markers will play an increasingly important role in assessment of response. In particular, bone resorption markers measuring collagen breakdown have potential as rapid, convenient, and inexpensive measures of response, with suppression of bone resorption into the normal range being an important aim of bone-specific treatments.