An autoimmune disorder occurs when the body’s immune system attacks and destroys healthy body tissue by mistake. Areas often affected by autoimmune disorders include blood vessels, connective tissues, joints, and skin, etc. The chemical advances in the 19th–20th centuries brought about the development of non-steroidal anti-inflammatory drugs (NSAIDs). Although effective in the treatment of inflammatory diseases, NSAIDs have some undesirable and adverse effect, such as ulcers, kidney injury, and bleeding in the gastrointestinal tract. Although initially identified as anti-tumor molecule, TNF is now considered as a pleiotropic cytokine which plays a major role in immune or inflammatory responses. Consequently, anti-TNF biologics, which are designed to block the biological function of TNF, have been developed for the therapy of autoimmune inflammatory diseases. The success of biologics for autoimmune diseases coupled with rapid advances in basic research has validated many immunology-relevant signaling pathways and uncovered new intracellular molecules to target for potential new drug agents that can enter the cell. For example, many small chemicals or macrolide derivatives that can inhibit immunoproteasome, nucleus output proteins, NF-kB, and TNF-alpha have the potential to be developed as the drugs to treat the autoimmune inflammatory diseases and chronic inflammatory diseases.