Rheumatoid Arthritis is a chronic progressive inflammatory auto-immune disease in which the immune system of the body attacks its cartilage and joints lining. It not only affects synovial joints but also many other sites including heart, blood vessels, and skins. It is more common in females than in males. The exact cause of rheumatoid arthritis is not well established but the hypothesis reported in the literature is that in the development stage of the disease, both genetics and environmental factors can play an inciting role. Along with these factors alteration in the normal physiology of enzymatic action, acts as a trigger to develop this condition. Numerous signaling pathways involved in the pathogenesis of Rheumatoid Arthritis involves activation of mitogen-activated protein kinase, kinases Janus family, P-38 Mitogen-Activated Protein Kinase, Nuclear Factor-kappa B. Interleukin-1 to play a proinflammatory cytokine that plays an important role in inflammation in RA. These are also associated with an increase in neutrophil, macrophage and lymphocytic chemotaxis, mast cell degranulation, activation, maturation and survival of T-cells and B-cells activated. These signaling pathways also show that p38α downregulation in myeloid cells exacerbates the severity of symptoms of arthritis. Thus, present review carters about the detail of different signaling pathways and their role in rheumatoid arthritis.