Viscosupplementation by means of intra-articular injections of hyaluronic acid has been used to treat osteoarthritis of the knee. The proposed mechanisms of action result from the physical properties of hyaluronic acid, as well as from its anti-inflammatory, anabolic, local analgesic, and chrondroprotective effects. Adverse reactions from hyaluronic acid injections into the knee occurred in 8.3% of the 336 patients treated in one study, but at a rate of less than 3% per injection. Reactions were almost always local and generally resolved over 1 to 2 days. Hyaluronic acid injections were approved by the US Food and Drug Administration as a medical device; thus, the level of efficacy demonstrated is less than might have been required for approval as a drug. Several studies have failed to show statistically significant benefit compared with placebo. Furthermore, the treatment is relatively expensive; the cost of the drug for a series of injections is more than $500 per knee. Therefore, widespread use of these agents should be limited until more convincing data on their efficacy are available from well-designed clinical trials.