Among chronic inflammatory diseases, rheumatoid arthritis is a common inflammatory and destructive arthropathy, characterized by the release of potent proinflammatory cytokines mostly TNFa and IL-1, which both mediate systemic effects and contribute to joint destruction. Many therapeutic agents have been proposed to antagonise these cytokines, among which monoclonal antibodies. Thus twenty years ago the anti-TNFa infliximab was the first monoclonal antibody to be proposed in a non-cancerous indication, rheumatoid arthritis. Since then, several other monoclonal antibodies and/or antagonists either targeting cytokines (IL-1, IL-6, RANKL), but also immune cellular effectors T and B cells, have been evaluated not only in rheumatoid arthritis, but also in systemic lupus, Crohn's disease, multiple sclerosis, or ankylosing spondylitis. Clinical benefit has been unambiguously demonstrated, but before these novel molecules enter routine clinical practice, several parameters will have to be accurately documented such as their safety, long term efficacy, and economical cost.