Osteoarthritis (OA) is the most common form of musculoskeletal disorders and a cause of major disability. The traditional purpose of pharmacological intervention in this disease is to alleviate symptoms such as pain and restricted mobility, through the use of analgesics, mainly from the group of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and substances belonging to the SYSADOA group. Best described and most widely used substances belonging to SYSADOA group are glucosamine sulfate (GS) and chondroitin sulfate (CS). These substances are the main building block of joint cartilage and the synovial fluid. Based in in vitro studies, it is known that both GS and CS can affect cartilage tissue by complex proanabolic, anti-degenerative and anti-inflammatory actions, and the clinical studies provide supporting data. Both the CS and the GS show efficacy in treatment of symptoms of OA and exert positive impact on the structure of the joints. Furthermore, potential synergistic effect between CS and GS seen in in vitro studies is also confirmed in the clinical setting. In GAIT clinical trial the analysis of a subgroup of patients with medium to severe OA strongly supports the idea of synergy between the CS and GS. Only in a group which used both compounds significant therapeutic effects was observed (decrease in pain and better joint function). Accumulating evidence indicates that combined treatment of glucosamine and chondroitin may bring more health benefits than GS or CS as monotherapy.