Women with advanced breast cancer often develop bone metastases that are associated with skeletal-related events (SREs), which reduce quality of life and increase the risk of death. Because patients who experience one SRE are more likely to experience subsequent events, the goal of therapy is to preserve quality of life by delaying the onset of the first SRE and reducing the incidence of subsequent SREs. Bisphosphonates are used for clinical management of malignant bone disease, and data suggest that early treatment (e.g., before bone pain) may confer additional clinical benefit. Furthermore, data from subsets of zoledronic acid trials suggest that long-term bisphosphonate therapy may provide sustained clinical benefit throughout the disease course. Bisphosphonates are generally safe and well tolerated; adverse events are more often mild and transient. Zoledronic acid has proven efficacy for reducing risk of SREs, and ongoing studies are under way to evaluate customized treatment schedules.