Hyaluronan (HA) is a variable length, long-chain polysaccharide containing repeating disaccharide units of glucuronic acid and n-acetylglucosamine. Long considered a relatively inert component of the extracellular matrix, HA is now coming under scrutiny as a potential therapeutic agent for a number of different diseases, based on its recently discovered role in modulating inflammation. The effect of HA on the inflammatory response appears to be related to its molecular size, with larger polysaccharide chains having anti-inflammatory activity and smaller ones having proinflammatory properties. This dichotomous behavior presents a challenge to investigators seeking to harness the beneficial effects of this molecule. Rapid breakdown of therapeutically administered HA into smaller fragments may conceivably cause further injury to diseased tissues. With this limitation in mind, the authors discuss their own use of HA to treat experimentally induced lung disease, then suggest possible ways of maximizing the therapeutic potential of this molecule.