Treatment with intra-articular viscosupplementation with hyaluronan (hyaluronic acid) and its derivatives is an important component of the management of osteoarthritis (OA) of the knee. Several intra-articular hyaluronan formulations are now available that vary in their physical properties, duration of effect and treatment schedules. Although aspects regarding their mechanism of action are not completely understood, numerous clinical trials, systematic reviews and meta-analyses have confirmed the efficacy of intra-articular hyaluronan therapies for relieving OA-related pain and improving joint function. Data indicate that intra-articular hyaluronan preparations provide OA pain relief that is comparable to or greater than that observed with conventional treatment, NSAID medications, intra-articular corticosteroids, arthroscopic lavage, physical therapy and exercise. Other studies indicate that multiple courses of hyaluronan are effective. Intra-articular hyaluronan formulations are well tolerated and are associated with a low incidence of adverse effects, usually localised to the injected joint. Local adverse events associated with intra-articular hyaluronan products are typically mild to moderate in severity, benign and transient, although their aetiology is unknown. The cost effectiveness of intra-articular hyaluronan has been demonstrated, but only in a limited number of studies. Cost savings with intra-articular hyaluronan can also be realised with reduction of NSAID medication use and the possibility of delaying total knee replacement, which can reduce the need for costly revision procedures. Because different intra-articular hyaluronan formulations require different numbers of injections and office visits, are associated with variable treatment costs, and provide varying degrees of efficacy, not all intra-articular hyaluronan formulations may be equally cost effective over time.