Systemic lupus erythematosus (SLE) is a multisystemic disease characterized by profound alterations of the immune system that contribute to inflammation and tissue damage. The diverse presentations of SLE range from rash and arthritis through anemia and thrombocytopenia to serositis, nephritis, seizures, and psychosis. SLE should be part of the differential diagnosis in virtually any patient presenting with one of these clinical problems, especially in female patients between 15 and 50 years of age. Since 90% of patients with SLE are female, an important role for sex hormones seems likely, but a protective role for male hormones is also possible. Pathogenic auto-antibodies are the primary cause of tissue damage in patients with SLE. The production of these antibodies arises by means of complex mechanisms involving every key facet of the immune system. There are no diagnostic criteria, only classification criteria. In order to consider SLE for research practice, the patient must present at least four of 11 criteria established by the American College of Rheumatology (ACR). Many different elements of the system are potential targets for therapeutic drugs in SLE. The treatment involves immunosuppressive medications like high-dose of corticosteroids, azathioprine, and cyclophosphamide. Mycophenolate mofetil and rituximab have been used in association with corticosteroids (oral or intravenous pulse therapy) in SLE patients. Besides, anti-malarial medications are used not only to control disease, but also to improve survival and to reduce the risk of thrombosis. The aim of this review is to describe symptoms of SLE that may vary from rash and arthritis through seizures, and psychosis. We will also include a review on current treatment and new medications. © 2011 Nova Science Publishers, Inc. 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