Rheumatoid arthritis (RA) is an autoimmune disease that leads to inflammation and destruction of synovial joints. Despite the broad spectrum of antirheumatic drugs, this heterogeneous disease is still not well controlled in up to 30% of patients. Here, we discuss two pathways that are regarded as interesting novel therapeutic targets in the field of rheumatology: the Janus kinase (JAK) pathway and the T helper-17 (Th17) pathway [including interleukin (IL)-17, IL-21, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF)]. We also review the therapy potential of biologicals and small-molecule inhibitors blocking these pathways. Advances in combination therapy in addition to progress in biomarker screening will help us to further achieve effective and personalized healthcare for patients with RA.