As evidenced by publication of a new set of guidelines for the treatment of osteoarthritis (OA) by the American College of Rheumatology after only 5 years, modalities available for the management of OA have undergone significant changes. New therapeutic approaches include the use of cyclo-oxygenase-2 inhibitors, and intra-articular hyaluronans (HA). HA, found in a number of body tissues, is altered in the presence of osteoarthritis with decreased molecular weight and concentration resulting in impaired viscoelasticity. Hyaluronan preparations have been shown to decrease pain and increase function in patients with osteoarthritis of the knee. Mechanisms of therapeutic effect include restoration of more normal synovial fluid with improved viscoelasticity, effects on cartilage biosynthesis and degradation, anti-inflammatory effects, and direct analgesic effects. Studies in animal models, and preliminary studies in humans suggest that hyaluronans may have a structure-modifying effect in OA. Hyaluronans represent a substantive addition to the therapeutic armamentarium in osteoarthritis.