Bisphosphonates have an established role in treating tumor-induced hypercalcemia and decreasing the incidence of skeletal-related events. Recent data suggest that these agents may also prevent skeletal metastases. This review explains how cancer metastasizes to bone and how bisphosphonates may block this process, with a summary of clinical trials supporting the use of bisphosphonates to treat and prevent bone metastases. For skeletal metastases in patients with breast cancer, multiple myeloma, or other solid tumors, bisphosphonates are important adjuncts to systemic therapy. Despite promising results in metastatic prostate cancer, additional trials are needed before bisphosphonates become part of standard treatment in this setting. Ongoing trials are evaluating the preventive role of the third-generation bisphosphonates in breast cancer patients. Until the results of these trials are presented, bisphosphonates should only become a component of adjuvant treatment in the context of a clinical trial. Bone loss, a common consequence of cancer treatment, should be treated with the usual measures indicated for the management of osteoporosis, including bisphosphonates.