Hyaluronan is an unbiquitous glycosaminoglycan present in most tissues. Under homeostatic conditions hyaluronan exists as a high molecular mass polymer that has important roles in tissue structural integrity. Under conditions of stress such as following tissue injury, hyaluronan becomes depolymerized and lower molecular mass polymers are generated. The biological properties of these hyaluronan fragments appear to be distinct from the larger precursor molecules. This review examines the biological role of hyaluronan fragments in tissue injury and repair.