Zoledronic acid has been marketed for the past 5 years for the treatment of hypercalcemia of malignancy and malignant bone disease in patients with multiple myeloma or a broad range of solid tumors. The safety profile of zoledronic acid in this patient population is well established from the databases of several large, randomized, Phase III trials and postmarketing clinical experience. Zoledronic acid is well tolerated, with predictable side effects, primarily transient flu-like symptoms, which are manageable with standard treatment. Renal monitoring is recommended, with dose reductions for patients with renal dysfunction. Monitoring for electrolyte imbalance is also important as is calcium and vitamin D supplementation. Ocular complications are rare, and osteonecrosis of the jaw is uncommon and might be avoidable with appropriate dental care.