In the mid-1980s, new molecular tools enabled the biology of cytokine expression and regulation to be studied. Our group uncovered a TNF-dependent cascade in active rheumatoid synovium, suggesting that TNF might be a therapeutic target; this concept was supported in an animal model of the disease. The proof of concept was a series of clinical trials, which have led to marked changes in the therapy of human rheumatoid arthritis and subsequently of other diseases. The work with TNF clearly demonstrated the importance of cytokines in medicine as well as the capacity of mAbs (or receptor fusion proteins) to be used long-term in large populations, thus changing the therapeutic landscape.