Diverse strategies to develop novel treatments for rheumatoid arthritis which specifically target those patients who do not respond to available medications, including biologics, are currently being explored. New potential therapeutic approaches which may become available as part of standard therapeutic regimens include the propagation of regulatory T cells and-in the future-of regulatory B cells. New biologic disease-modifying antirheumatic drugs (b-DMARDs) against interleukin-17 and -6, granulocyte-macrophage colony-stimulating factor, and complement component 5 are now standard components of clinical treatment programs. In addition, recent data indicate that bispecific monoclonal antibody therapies may be more effective than monoclonal antibody monotherapies. It is also becoming apparent that the use of more toxic b-DMARDs against B cells, a therapeutic strategy already being applied in the treatment of hematological diseases, may also be efficacious for treating B cell-mediated autoimmune diseases. Undoubtedly, more small molecules will be developed in the future, and combination therapies with, for example, kinase inhibitors and b-DMARDs, will most likely be tested. Finally, immunoproteasome inhibitors will become available for patients with B cell-mediated autoimmunities, which are refractory to currently available treatment options. The new and exciting extension of current treatment options for rheumatoid arthritis, biosimilars, will not be discussed in this review as details on these agents are available in recently published reports.