In women who develop bone metastases from breast cancer (BC), interactions between tumor cells and osteoclasts within the bone lead to localized bone destruction and increase the risk of skeletal-related events (SREs). Bisphosphonates inhibit osteoclast-mediated bone resorption, and have been used extensively for treating post-menopausal osteoporosis and reducing the risk of SREs in patients with bone metastases. A number of clinical trials in women with early stage BC have demonstrated that adding bisphosphonates to adjuvant endocrine therapy can prevent bone loss and may prevent disease recurrence and improve disease-free survival. In women with bone metastases from BC, bisphosphonates have demonstrated efficacy for reducing skeletal morbidity and pain and improving quality of life. Recent economic analyses have demonstrated that bisphosphonate therapy is a cost-effective use of healthcare resources. This review summarizes the available data for bisphosphonate benefits in both the adjuvant and metastatic settings in the context of evolving clinical practice.