Conventional management of metastatic bone disease involves local and systemic therapies in various combinations, along with symptomatic management to provide optimal care. In recent years, it has become clear that adding bisphosphonates to these treatments reduces the incidence and severity of skeletal complications. Bisphosphonates can also relieve metastatic bone pain and improve quality of life, although the extent to which they have demonstrated these effects may differ between agents. While bisphosphonates are the standard of care for the treatment of bone metastases, clinical trials are investigating additional indications for these agents, including the use of intensive dosing regimens for the relief of severe or opioid-resistant metastatic bone pain and adjuvant treatment for the prevention of bone metastases and cancer treatment-induced bone loss. Current and future indications demand effective, well-tolerated and convenient bisphosphonates, and the benefits of different drugs must be balanced against their limitations. The cost-effectiveness of bisphosphonate treatment is also a consideration, given the high economic burden of metastatic bone disease from breast cancer.