Ophthalmic disorders are amid the most common pathologies worldwide. In this regard, hyaluronan (HA) has gained widespread use in eye surgeries and treatment of eye diseases. HA-based materials are well tolerated and show excellent biocompatibility. Therefore, HA is a sought-after component of ophthalmic formulations. However, several parameters have to be adjusted to reach an optimal performance and effectiveness. The complexity of HA properties represents a major challenge for biological and structural characterization. This review covers fundamental aspects and recent developments in HA ophthalmic research. Biological mechanisms underlying the health benefits of HA and their potential therapeutic applications are elaborated. Furthermore, current pharmacokinetic and safety studies are discussed. Noticeably, the benefits of chemical modification and processed HA forms are described to broaden the applications of this unique polysaccharide. The current research challenges and prospects are also outlined and discussed.Copyright © 2021 Elsevier Ltd. All rights reserved.