Autoimmune inflammatory diseases such as rheumatoid arthritis are based on (i) an initial transition of clinically silent autoimmunity to clinically apparent inflammation, (ii) the building-up of a robust systemic inflammatory process and (iii) the maintenance of this process by blocking naturally occurring resolution mechanisms. These different aspects of chronic inflammatory diseases are not necessarily controlled by the same cytokines. Recent data for instance suggest that the transition from autoimmunity to inflammation is essentially governed by IL-23, which controls the pathogenicity of autoantibodies and their cytokine producing potential. Essential effector cytokines in this process are IL-21 and IL-22, which influence the sialylation and thereby the effector function of antibodies. While the processes controlling initialization of the rheumatoid arthritis have only been defined recently, the factors that control systemic inflammation are well defined since several years with IL-6 and TNF-alpha being the key effector cytokines. While TNF-alpha controls inflammatory processes in many different chronic inflammatory diseases including rheumatoid arthritis, Crohn´s disease and psoriasis, IL-6 seems to be more specific for rheumatoid arthritis controlling both the local inflammatory process in the joint but also the systemic consequences of the disease. Finally, rheumatoid arthritis is characterized by a remarkable chronicity with the virtual lack of physiological resolution processes taking place. The resolution process of rheumatoid arthritis has been enigmatic to date. Recent data, however, have shown that IL-9 represents the essential pro-resolving cytokine for arthritis. IL-9 is a key factor for the expansion of type 2 innate lymphoid cells, which activate the regulatory T cells and allow the resolution of joint inflammation. This phase-orientated disease control by cytokines suggests that future treatment of RA, in particular selective cytokine inhibition may be more tailored to different phases of the disease. On the other hand, therapeutic concepts, which inhibit multiple cytokines, e.g. such as those targeted intracellular signaling pathways, may prove as beneficial throughout the entire disease process.