The treatment of Paget's disease of bone (PDB) aims at suppression of abnormal bone turnover and bisphosphonates (BPs) are currently the drugs of choice. Zoledronic acid, a third-generation nitrogen-containing BPs, is the newest BP approved for PDB and is administered by a single intravenous infusion. In vitro zoledronic acid has higher binding affinity for hydroxyapatite and is a stronger inhibitor of farnesyl pyrophosphate synthase compared with other BPs. In vivo zoledronic acid improves symptoms, normalizes bone turnover markers and scintigraphic imaging in the majority of patients, and maintains remission of PDB longer than other BPs. This review summarizes available data on the pathogenesis, epidemiology, clinical manifestation, biochemical assessment and management of PDB, giving special attention to the treatment of PDB with zoledronic acid, based on current evidence.