Biological therapies directed at proinflammatory cytokines have irrevocably changed the landscape of treatment of rheumatoid arthritis (RA) and other autoimmune diseases. With the advances in our knowledge in cytokine signalling, the question emerges whether targeting intracellular signalling might also be a safe and efficacious strategy. Janus kinases or Jaks are critical for a large family of cytokines and the first Jak inhibitors has been approved by the FDA. It is therefore timely to consider this new category of drugs and reflect on their potential roles, present and future, in the treatment of RA and related disorders.