Painful and life-threatening skeletal complications are common in patients with advanced cancer metastatic to bone. Patients with breast cancer and multiple myeloma who survive for 2 or more years after developing bone metastases/lesions are at chronic risk for skeletal complications. Patients with prostate cancer and other solid tumors are also at high risk for skeletal complications, and, until recently, no effective treatment had been identified. Zoledronic acid, a new-generation bisphosphonate, was recently shown to be safe and effective as treatment for the prevention of skeletal complications in three randomized, phase III trials involving more than 3000 patients with multiple myeloma, breast, prostate, and lung cancers, and other solid tumors. Zoledronic acid (4 mg) was at least as effective as pamidronate (90 mg) in preventing skeletal complications in the overall study population of patients with breast cancer and multiple myeloma and was superior to pamidronate in the subset of over 1000 patients with breast cancer. In patients with solid tumors, including prostate cancer and lung cancer, zoledronic acid significantly reduced the incidence and delayed the onset of skeletal complications compared with placebo. Zoledronic acid is the first bisphosphonate with broad clinical utility and may become the preferred bisphosphonate for the treatment of bone metastases in patients with advanced cancers.