New approaches for antirheumatic therapy are firmly based on current knowledge of immunopathogenic processes. Specific immunotherapy is directed at the treatment of the disease per se and not the production of generalized immunosuppression with its unwanted side-effects. The three targets against which specific immunotherapy is directed are the T cell receptor, the HLA antigen linked to the disease and the antigenic peptide involved in the initiation and/or persistence of the disease. Therapies directed against lymphokines, monokines and cytokines produced during the chronic immune-mediated inflammation are also being developed but they may be unsuccessful not only because of the great redundancy inbuilt into the inflammatory response but also because they would produce too general a response with possibilities of harmful side-effects. Specific immunotherapy at present is largely through the use of monoclonal antibodies directed against a variety of T cell membrane antigens such as CD4, CD7 and the interleukin 2 receptor. A possible therapy is monoclonal antibodies, directed against the HLA molecule involved in the aetiopathogenesis of disease. The use of disease-causing T cell lines or clones as vaccines or therapeutic agents has solid experimental support and studies are in progress in patients with rheumatoid arthritis using T cell lines grown from synovial fluid aspirates. If successful, such therapy could be modified to the use of short peptide fragments from the relevant T cell receptor. T cells recognize antigenic peptides presented on the surface of antigen-presenting cells within a groove formed by the HLA molecule. Displacement of disease-inducing antigenic peptides by engineered 'neutral' peptides could offer a very precise form of immunotherapy. Many of these approaches are based on the hypothesis that transient but effective switching-off of the disease process may allow immunoregulatory circuits, as yet poorly defined, to come into play to permanently cure the disease. Many such therapies are in the offing. It may be that they have to be used in various combinations in order to achieve cure. For this complex and time-consuming task to attain that desired consummation, co-operative interaction between many clinicians, basic scientists and patients will be required. It is to that cooperation that we dedicate this chapter on new approaches for antirheumatic therapy.