Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disorder, characterized by synovitis and severe joint destruction. Many mechanisms are considered to be implicated in the development and progression of the disease. It may be important to understand differences in the pathogenesis of RA at various stages of its process. Early autoimmune changes begin before the onset of clinical arthritis. During this period, various autoantibodies such as rheumatoid factor and anticyclic citrullinated peptide antibody can be produced by the interaction between B and T cell activated by aberrant immune responses, triggered by external or self antigens. This is followed by a local inflammatory transitional phase, in which complex biochemical processes are involved in molecular and structural changes of the joint. The primary inflammatory site is the synovium. Synovial infiltration with mononuclear cells, especially CD4⁺ T cells, macrophages, and B cells leads to an articular, pathologic phase. In this phase, proinflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6 as well as inflammatory mediators such as prostaglandin E2 and proteases can be produced by various cell to cell interaction occuring in the synovium, which may finally result in the destruction of synovium, cartilage and bone. Although the pathogenesis of RA is intricate and remains unclear, understanding and identifying its pathogenesis is important in revealing the appropriate therapeutic target that may lead to significant clinical benefits.