Current treatments for osteoarthritis (OA) are mainly targeted towards providing short-term symptom relief. The focus in the development of disease-modifying drugs has been on therapies that modify cartilage directly. Recent research has highlighted the importance of subchondral bone as a target for therapeutic intervention and disease modification. At the subchondral level, affected joints have decreased bone mineral content and quality. In addition, increased bone turnover has been observed at levels similar to those in patients with osteoporosis. Consequently, the potential benefits of drugs that alter bone metabolism are being examined in this disease, in particular, the antiresorptive agents, bisphosphonates. Results from pre-clinical studies have shown promising results for these compounds. Although the mechanism of action remains unclear, comparative studies indicate that this activity may be unique to the specific structure of the bisphosphonate, rather than representative of a class effect. Clinical studies are now under way to determine the efficacy and safety of bisphosphonates which may offer new therapeutic options in the treatment of OA.