We provide the basics for the clinician who might be called on to consider the diagnosis of diseases such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) in their practice. We will emphasize clinical recognition and first-line laboratory testing. Only characteristics of the classic rheumatic inflammatory diseases, RA, SLE, Sjögren syndrome, scleroderma, and dermatomyositis/polymyositis, will be covered. In the past decade, RA is the only disease for which treatment has substantially improved. The treatment of RA has been revolutionized by the use of methotrexate and, more recently, tumor necrosis factor inhibitors. The goal of RA treatment today is to induce a complete remission as early as possible in the disease process, with the mantra being “elimination of synovitis equals elimination of joint destruction.” The hope is that if the major mediators of Sjögren syndrome or SLE or scleroderma can be identified and then blocked, as in the example of tumor necrosis factor inhibitors in RA, more specific treatments will become available. Thus, RA has become an excellent model of this evolving paradigm. Through the identification of major mediators in its pathogenesis, novel and highly efficacious therapeutic agents have been developed. (J Allergy Clin Immunol 2003;111:S593-601.)