Treatment for rheumatoid arthritis (RA) is a fast-moving field for the past 4 decades. In the 1970s, there were only gold preparation, methotrexate and D-penicillamine that were regarded as disease modifying anti-rheumatic drugs (DMARDs). Today, as the gold preparation becoming obsolete, there are many new agents with protean mechanisms of action and attenuated adverse effects adding on the arms of therapy. The milestone of these agents was the introduction of infliximab and etanercept in the turn of this century. These so-called “biologicals” or “biologics” work almost exclusively on the immune system and have very little effect on other cells in the body. With the combination of conventional non-biologic DMARDs, individual “biologics” has shown a powerful effect in abolishing the catastrophic outcome of advanced RA. More recently, the emerging evidence has indicated that other than blockade of the immune system or proinflammatory cytokines there are novel subcellular pathways that can be picked up as therapeutic targets. A representative way of these remedies is inhibition of the Janus kinase (JAK) – Signal transducers and activators of transcription (STAT) pathway. In this mini-review, the recent advances in the production of humanized anti-cytokine agents and the new therapeutic agent targeting JAK-STAT pathway will be briefly discussed.