While the association between obesity and osteoarthritis used to be solely regarded as a result of increased mechanical loading, systemic factors also likely play a role in the pathophysiology of osteoarthritis. Nutrient excess leading to obesity may result in lipotoxicity, which might be involved in the development of osteoarthritis. The different fatty acid types have distinct effects on inflammation. This review focusses on the currently available studies, summarizing the effects of the different fatty acid types on osteoarthritis and involved joint tissues. In animal studies omega-3 polyunsaturated fatty acids reduced the expression of inflammatory markers, cartilage degradation and oxidative stress in chondrocytes. In contrast, these markers were increased upon omega-6 polyunsaturated fatty acid and saturated fatty acid stimulation. Additionally, a decrease in pain and dysfunction was observed upon omega-3 supplementation in cats and dogs. In line, most human in vitro studies show pro-apoptotic and pro-inflammatory actions of saturated fatty acids. While all polyunsaturated fatty acids reduced markers of oxidative stress, omega-3 polyunsaturated fatty acids additionally decreased prostaglandin production. Human intervention studies with omega-3 polyunsaturated fatty acid supplementation may indicate a beneficial effect on pain and function and might be associated with less structural damage. In contrast, an adverse effect of saturated fatty acids on osteoarthritis has been observed. Monounsaturated fatty acids have been infrequently studied and findings are inconclusive. Existing studies indicate a promising effect of especially omega-3 polyunsaturated fatty acids on osteoarthritis signs and symptoms. However, more human intervention studies are warranted to draw robust conclusions.