Tumor necrosis factor-alpha, acting through its receptors expressed on all cells of the body, is a key mediator of inflammation and immunity. However, its overproduction may also lead to pathologic changes. The latter situation occurs often in chronic inflammatory diseases such as rheumatoid arthritis. The concept suggesting tumor necrosis factor-alpha as a potential target emerged from experiments showing its key role in inducing many cytokines and mediators of inflammation. Several clinical trials targeting this cytokine in rheumatoid arthritis patients with a novel group of anti-tumor necrosis factor agents demonstrated reduced synovial inflammation and inhibition of bone and cartilage degradation. In addition to the therapeutic value of anti-tumor necrosis factor, analysis of laboratory changes not only proved the concept but provided new data, continuously expanding our understanding of the role of tumor necrosis factor-alpha in the pathogenesis of many diseases. These laboratory measures may also help the earlier identification of rheumatoid arthritis patients who have a less satisfactory response to this therapy.