Rheumatoid arthritis (RA) is an inflammatory disorder associated with chronic synovitis, eventually leading to cartilage and bone destruction in the joints. Synovitis is associated with the activation of various cells in the synovium including synovial lining cells, interstitial macrophages, endothelial cells, lymphocytes, and fibroblasts. The key mechanisms underlying synovitis include inflammatory cell adhesion and activation, the production of mediators (such as cytokines, chemokines, and growth factors), angiogenesis, joint destruction, fibrosis, and bone resorption. These important events, as well as the role of inflammatory cells, cell surface molecules, and soluble mediators are updated and discussed in this review. Some aspects and strategies of current or future immunotherapy are also discussed because these animal and human trials provide information on the pathogenesis of inflammatory synovitis.