Hyaluronic acid is an important naturally occurring polysaccharide present in extracellular matrices. The network-forming, viscoelastic and the charge characteristics of hyaluronic acid are important to many biochemical functions of living tissues. Its involvement in many diseases such as cancer, arthritis and osteoporosis, and the fact that it has specific protein receptors present on the cell surfaces, has given new impetus in drug design and synthesis of hyaluronic acid-drug conjugates. As a general arrangement, the review will focus on structure and conformation of hyaluronic acid, its chemistry and chemical methodologies that have led to a number of important hyaluronic-drug conjugates. INTRODUCTION: Hyaluronic acid (also known as hyaluronan, 1; henceforth abbreviated as HA) is a naturally occurring polysaccharide of a linear repeating disaccharide unit consisting of β-(1→4)linked D-glucopyranuronic acid and β-(1→3)linked 2-acetamido-2-deoxy-D-glucopyranose, which is present in extracellular matrices, the synovial fluid of joints, and scaffolding that comprises cartilage. The unique physico-chemical characteristics, its mechanism of synthesis and its size set hyaluronic acid apart from other glycosaminoglycans. The network-forming, viscoelastic and its charge characteristics are important to many biochemical properties of living tissues.