Intra-articular administration of hyaluronic acid (Hyaluronan) (HA) is now gaining widespread acceptance for the treatment of osteoarthritis (OA), even though little is known of its mechanism of action. In vitro and in vivo studies have shown that HA is able to modulate a variety of cellular functions, suppress the activities of pro-inflammatory mediators and can attenuate the nociceptive response in arthritic joints. However, recent studies with animal models of non-inflammatory OA have questioned the ability of HA to protect articular cartilage degeneration directly. The objective of this review is to examine some aspects of HA chemistry and pharmacology in relation to its interactions with cells, cartilage and the components of synovial fluid.