Since bone metastases in advanced cancer are common and frequently lead to skeletal-related morbid complications, their treatment remains a major challenge in cancer therapy. Bisphosphonates not only significantly decreased the odds ratios for fracture, need for radiotherapy, and incidence of hypercalcemia, but also had proven ability in the preservation of the 3D microstructure of bone that is responsible for bone stability. Bisphosphonates are well tolerated and have a very low incidence of serious side effects. Consequently, bisphosphonates have become the standard of care for the treatment of malignant bone disease. Benefits of bisphosphonate treatment appears to be more pronounced with longer treatment, indicating that they should be continued until no longer clinically relevant. As this advice has substantial implications on resources, it is essential that the use of bisphosphonates is evidence based.