Zoledronic acid (Reclast, Aclasta, Zometa) is an intravenous, highly potent amino-bisphosphonate approved worldwide, including in the USA, EU and Japan for use in patients with primary or secondary osteoporosis or low bone mass (approved indications vary between countries). Its high affinity to and long half-life in bone, and long duration of action allow for once-yearly administration, which has the potential to improve adherence to therapy. Zoledronic acid once yearly for up to 3 years improved bone mineral density (BMD) at several skeletal sites, reduced fracture risk and bone turnover, and/or preserved bone structure and mass relative to placebo in clinical studies in patients with primary or secondary osteoporosis. While additional benefits were seen when treatment was continued for up to 6 years, as evidenced by a reduced risk of vertebral fractures and higher BMD relative to 3 years’ therapy, there was the minimal advantage of treatment beyond 6 years. Therefore, in patients with low fracture risk, treatment discontinuation should be considered after approximately 5 years’ therapy. Zoledronic acid administered annually or once in 2 years was also effective in preventing bone loss in patients with low bone mass. Zoledronic acid was generally well tolerated, with the most common adverse events (AEs) being transient, mild-to-moderate post-infusion symptoms, which decreased with subsequent infusions.