This review addresses the area of study that defines the field of surface modification of biomedical materials and devices by hyaluronan (HA), as related to the exploitation of HA biological properties. To provide a comprehensive view of the subject matter, initial sections give a quick introduction to basic information on HA-protein and HA-cell interactions, together with some discussion on the bioactive role of HA in wound healing and related phenomena. This is followed by a description of current theories that correlate HA properties to its molecular structure in aqueous media, underlying how HA molecular details are crucial for its biological interaction and role. Finally, existing approaches to surface modification by HA are reviewed, stressing the need for HA-surface engineering founded on the knowledge and control of the surface-linked HA molecular conformation at the solid/aqueous interface.