Major advances in basic-science rheumatology research have been achieved in various fields including molecular techniques, signaling pathways, experimental strategies, and in several bench-to-bedside approaches. Using laser-mediated microdissection, small areas of interest in a given diseased tissue can be analyzed in a high-resolution setting. Molecular imaging, especially the combination of labeled molecules such as albumin that are metabolized by active cells together with smart probes, can be used to visualize key mechanisms in rheumatoid synovial tissue in a real-time setting. Recently discovered microparticles and Toll-like receptors have been found to be dominant players in innate immunity-driven inflammation and destruction in the rheumatoid joint. Moreover, long-lived plasma cells appear to be a major factor in resistance to immunosuppressive drugs in autoimmune disease. With regard to bench-to-bedside strategies, various targeted therapies including various gene transfer strategies yielded promising preclinical results.