Hyaluronan has a very simple structure. It is a linear glycosaminoglycan composed of disaccharide units of GlcNAc and d-glucuronic acid with alternating ?-1,4 and ?-1,3 glycosidic bonds that can be repeated 20,000 or more times, a molecular mass >8 million Da, and a length >20 ?m. However, it has a very complex biology. It is a major, ubiquitous component of extracellular matrices involved in everything from fertilization, development, inflammations, to cancer. This JBC Review highlights some of these processes that were initiated through publications in the Journal of Biological Chemistry.