The ingress of inflammatory leukocytes into the synovium is important for the pathogenesis of rheumatoid arthritis. Soluble inflammatory mediators regulate the inflammatory, chemotactic, adhesive, angiogenic events, as well as osteopenia associated with this disease. In this review authors discuss the role of a number of inflammatory mediators, such as cytokines, chemokines and growth factors in these processes. The outcome of arthritis is highly dependent on the imbalance between pro-inflammatory and anti-inflammatory mediators. Cytokine-related research also has important clinical relevance. Many of these proteins are detectable in the serum of rheumatoid patients and may eventually serve as useful laboratory markers of disease activity. Antirheumatic therapy currently used for the treatment of rheumatoid arthritis is often limited. Therefore, we need to consider alternative therapeutic regimens, such as the inhibition of cytokines and other soluble mediators, in order to prevent severe joint destruction. While there are many complex interactions involving cytokine networks and cascades in the arthritic joint, there are promising attempts to eliminate a single cytokine in clinical trials, such as ablation of tumor necrosis factor-alpha. Hopefully, the study of cytokines and their networks will lead to specific immunomodulatory therapies that will benefit rheumatoid patients by preventing joint destruction.