Question: Should bisphosphonates be used in patients with bone metastases from breast cancer? Perspective: Evidence was selected and reviewed by a medical oncologist working with the Cancer Care Ontario Practice Guidelines Initiative Breast Cancer Disease Site Group. This practice guideline report has been reviewed and approved by the Breast Cancer Disease Site Group, which comprises surgeons, medical oncologists, radiation oncologists, epidemiologists, a pathologist, a medical sociologist, and community representatives. Outcomes: Pain and skeletal events were the primary outcomes of interest. Radiologic course, quality of life, toxicity, and survival were also considered. Results: Quality of Evidence. Evidence was obtained from three randomised controlled trials of clodronate and four of pamidronate which evaluated skeletal events and pain in patients with bone metastases from breast cancer. Evidence was also acquired from three trials of clodronate and one of pamidronate for the management of metastatic bone pain in patients with several types of cancer, including breast. Benefits: These trials show that once bone metastases are present oral clodronate or intravenous pamidronate can significantly reduce skeletal events and pain, when used concomitantly with first-line chemotherapy or hormonal therapy. The overall risk ratios were 0.72 (95% confidence interval [CI]: 0.60-0.87; p = 0.0006) for fractures and 0.61 (95% CI: 0.51-0.73; p < 0.00001) for the need for radiotherapy, demonstrating a significant effect in favour of treatment with bisphosphonates. Although intravenous clodronate has relieved bone pain in short-term studies, the optimal frequency of administration or its efficacy in reducing fractures and the need for radiation therapy has not been determined. Harms: Bisphosphonates appear to be well tolerated. With oral preparations, gastro-intestinal intolerance is the most common reason for non-compliance, but placebo-controlled trials found no difference between active therapy and placebo. Uveitis is a rare, but documented, complication requiring urgent referral to an ophthalmologist.