Chondroitin sulfate is an important structural component of cartilage and provides much of its resistance to compression. Along with glucosamine, chondroitin sulfate has become a widely used dietary supplement for treatment of osteoarthritis. The benefit of chondroitin sulfate in patients with osteoarthritis is likely the result of a number of effects including its anti-inflammatory activity, the stimulation of the synthesis of proteoglycans and hyaluronic acid, and the decrease in catabolic activity of chondrocytes inhibiting the synthesis of proteolytic enzymes, nitric oxide and other substances that contribute to damage cartilage matrix and cause death of articular chondrocytes. A recent review summarizes data from relevant reports describing the biochemical basis of the effect of chondroitin sulfate on osteoarthritis articular tissues. The rationale behind the use of chondroitin sulfate is based on the belief that osteoarthritis is associated with a local deficiency in some natural substances, including chondroitin sulfate. Recently, new mechanisms of action have been described for chondroitin sulfate. In an in vitro study, chondroitin sulfate reduced the IL-1β-induced nuclear factor-kB (Nf-kB) translocation in chondrocytes. In addition, chondroitin sulfate has recently shown a positive effect on osteoarthritic structural changes occurred in the subchondral bone.