Systemic lupus erythematosus (SLE) is an inflammatory chronic disease characterized by the presence of activated helper T-cells that induce a B-cell response, resulting in the secretion of pathogenic autoantibodies and the formation of immune complexes. SLE in children is a disease of low prevalence with a wide range of clinical manifestations, which means that the number of randomized controlled studies are few and usually involve a small number of patients. In recent years, new therapeutic agents have appeared and the role of older treatments has been clarified. Many of these treatments are designed to reduce inflammation. The spectrum is broad and ranges from traditional nonsteroidal anti-inflammatory drugs (NSAIDs) to cytotoxic agents that have anti-inflammatory effects. The current treatment of children or adults depends on the clinical expression of the disease. Minor manifestations usually respond to the administration of NSAIDs, low doses of corticosteroids, hydroxychloroquine, or methotrexate. Thalidomide could be used for refractory skin lesions. Major manifestations can endanger the patient's life and require early, aggressive treatment. Kidney disease and other manifestations have been related to the formation or deposit of tissular immune complexes. Therefore, for years the main aim of treatment has been to suppress the immune response. The immunosuppressant treatments used in children with SLE include high doses of corticosteroids, azathioprine, methotrexate, cyclosporine, and cyclophosphamide. Several combinations of medications have been used to obtain a rapid remission or to reduce the risk of toxicity of prolonged administration of cytotoxic agents. Intravenous gamma-globulin has been successfully used in the treatment of lupus nephritis, vasculitis, and acute thrombocytopenia. In spite of numerous published studies, the use of these drugs is still controversial. The immunosuppression achieved with these treatments is nonspecific, not always effective, and associated with significant toxicities; the most significant being growth retardation, accelerated atherosclerosis and severe infectious complications. The purpose of new biological therapies is to achieve specific immunosuppression, which makes it possible to design more effective and less toxic therapeutic strategies. Mycophenolate mofetil is a promising alternative in patients who do not respond to high doses of cyclophosphamide or azathioprine. Some recently developed monoclonal antibodies such as anti-CD40L or anti-IL-10, or other molecules such as LJP394 may prove useful in the near future. Finally, stem cell transplantation may be proposed in patients with severe juvenile-onset SLE who do not respond to any treatment.