: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which involves a pathological inflammatory response against articular cartilage in multiple joints throughout the body. It is a complex disorder associated with comorbidities such as depression, lymphoma, osteoporosis and cardiovascular disease (CVD), which significantly deteriorate patients’ quality of life and prognosis. This has ignited a large initiative to elucidate the physiopathology of RA, aiming to identify new therapeutic targets and approaches in its multidisciplinary management. Recently, various lipid bioactive products have been proposed to have an essential role in this process; including eicosanoids, specialized pro-resolving mediators, phospholipids/sphingolipids, and endocannabinoids. Dietary interventions using omega-3 polyunsaturated fatty acids or treatment with synthetic endocannabinoids agonists have been shown to significantly ameliorate RA symptoms. Indeed, the modulation of lipid metabolism may be crucial in the pathophysiology and treatment of autoimmune diseases.