New treatments for rheumatoid arthritis (RA) continue to emerge to meet unsatisfied needs of a significant number of patients. The development of new, oral biologic therapy is a significant step forward, although these drugs will require further evaluation in clinical settings before their true potential is appreciated. This new, oral biologic therapy has mostly focused on inhibition of intracellular signaling. These mechanisms and the available studies regarding the efficacy and safety of specific drugs which interfere with these mechanisms are the subject of this article.