Established and novel approaches to the pharmacologic management of systemic lupus erythematosus (SLE) are described. SLE is a chronic, multiple-organ-system inflammatory disorder associated with immune system dysfunction. Autoantibodies are produced that react with self-antigens, notably cell membranes and nuclear and cytoplasmic constituents. There are many clinical manifestations, including arthritis, arthralgia, myalgia, skin changes, photosensitivity reactions, fever, anemia, thrombocytopenia, proteinuria, and renal, CNS, and cardiopulmonary involvement. The disease characteristically fluctuates between remission and relapse. Survival has been improving because of new drug treatments and better diagnostic and serologic tests. Minor manifestations can be treated with less toxic agents, such as nonsteroidal anti-inflammatory drugs, sunscreens, topical and intralesional corticosteroids, and antimalarials. Aggressive therapy with high-dose corticosteroids or immunosuppressants is necessary in patients with worsening renal function (lupus nephritis). CNS lupus has responded to various degrees to dexamethasone, methylprednisolone, and cyclophosphamide. Other therapeutic options include methotrexate in corticosteroid-resistant SLE and cyclosporine. The use of monoclonal antibodies is under intensive study. As mortality due to SLE decreases, complications like cardiovascular problems are becoming more prominent; patients may require antihypertensives, cholesterol-lowering drugs, and hypoglycemic agents. The complexity and chronicity of SLE have led to diverse pharmacotherapeutic strategies based on the organ systems involved. Immunologic research may ultimately bring patients greater relief.