Hyaluronic acid is a mucopolysaccharide encountered in most body fluids and extracellular matrix. The aim of our review is to summarize current evidence about chemico-physical properties of hyaluronic acid, highlighting biomedical applications of hyaluronan derivatives. It is a glycosaminoglycan made of repeating disaccharide units containing a carboxylate group, four hydroxyl groups and one carboxylate group, with hydrophilic properties. Its particular structure with multiple coils forming an entangled network results in unique pseudoplastic and viscoelastic characteristics. Its viscous and elastic behavior, depending on the applied strain, makes hyaluronan widely applicable in biomedical field. The large amount of functions and applications is determined by the physico-chemical properties, which allows a polymorphism of the hyaluronic acid structures depending on the molecular weight variations, concentration and ionic status. It is currently used in ophthalmology, orthopedics and rheumatology, in plastic surgery, surgery and otolaryngology as well. Already widely used in clinical practice, hyaluronic acid proves to be often the best solution for difficult medical problems. Future developments in nanomedicine and drug delivery linked to hyaluronic acid are emerging.