Target of this paper is to focus on the current knowledge about viscosupplementation in the management of osteoarthritis. The molecular structure and the effects of hyaluronic acid derivates on mechanical, biochemical and cellular level are described. Since the exogenously introduced hyaluronic acid derivates stay on average only 10 to 20 hour in the synovial fluid and yet its effect continues over months, an additional effect is postulated: modulation of the activity of the different cells in the development and progression of the osteoarthritis (synoviocytes, chondrocytes, inflammatory cells), probably by direct effect on their specific receptors. These receptors play an important role in the migration, adhesion and activation of inflammatory cells, as well as maturation and differentiation of the chondrocytes for synthesizing the cartilage matrix. In experimental studies in vitro and in vivo an analgetic and anti-inflammatory effect of hyaluronic acid derivates was proven. These results were confirmed in clinical studies. An amelioration of symptoms was shown and a delay of disease progression seems possible. This therapy is well tolerated and complications are few. Further studies to determine the optimal dosage and product (low or high-molecular preparation), the possible combination with other therapies in ideal sequence and the effect in the different subtypes of population are needed.