Introduction: Chondroitin sulfate belongs to the group of symptomatic slow-acting drugs for osteoarthritis (SYSADOA). The efficacy of this drug on symptoms is similar to that of non-steroidal anti-inflammatory agents, the effect starting gradually but persisting after treatment suppression. Materials and methods: We analyzed randomized, double-blind clinical trials that compared the effect of chondroitin sulfate with that placebo and, in one trial, with sodium diclofenac (150 mg/day) in patients with knee and finger osteoarthritis treated for periods ranging from 3 to 36 months. Results: The results of all the clinical trials indicate that chondroitin sulfate is more effective (by approximately 50%, p < 0.05) than placebo in reducing spontaneous pain, increasing joint function, and reducing rescue medication; in addition overall patient and physician assessment was higher. Equally, the trials confirm the high safety profile of the drug. A new clinical trial conducted in 1,583 patients with knee osteoarthritis, which studied the effect of glucosamine (1,500 mg /day), chondroitin sulfate (1,200 mg /day) and their association in comparison with celecoxib (200 mg/ day) and placebo for 6 months found a significant reduction of joint swelling, with or without joint effusion, for the chondroitin sulfate group compared with the placebo group (p = 0.01). Conclusion: Chondroitin sulfate is a highly useful therapeutic tool for the treatment of osteoarthritis.