According to the 2005 US census, osteoarthritis (OA) was the leading cause of disability in the United States, affecting more than 50 million people. Current treatments are targeted at reducing symptoms of the inflammatory reaction that occurs after destruction of essential joint cartilage. However, these treatments do not prevent significant pain and activity restriction. We reviewed the literature to address claims that fish oil supplementation can prevent or decrease severity of OA. Our extensive search of databases covered all relevant terms related to omega-3-containing supplements and their effects on OA. We hypothesized there would be insufficient clinical studies to justify recommending supplementation to patients.Laboratory studies have shown that eicosapentaenoic acid and docosahexaenoic acid reduce proinflammatory mediators and increase joint lubrication in vitro. In addition, canine trials have shown clinically significant reductions in various symptom parameters. Results of human clinical trials have not been consistently significant. Well-designed clinical trials are needed to substantiate or refute the potential benefit of fish oils in OA treatment. Long-term studies are needed to assess the possibility of prevention. In addition, standardization of the fish oil industry is needed for consistency of therapy.