Systemic lupus erythematosus (SLE) is a disorder that primarily affects young to middle-aged women. It is a complex multisystem disease that can have very varied presentations. Typical manifestations of SLE include rash, oral ulcers, arthritis, Raynaud's phenomenon, alopecia, pleuropericarditis, and renal and central nervous system disease. However, the entire constellation of symptoms often is not present, and definitive diagnosis in early or atypical SLE can sometimes be difficult. Although the diagnosis of SLE is primarily clinical, it is often supported by the presence of specific autoantibodies. Recognition of the various signs and symptoms of SLE will allow the primary care physician to order appropriate screening tests and more specific serologies to help confirm the diagnosis. The antinuclear antibody is a useful screening test as it is found in more than 95 percent of patients with SLE, but its use is limited by its lack of specificity. Anti-double stranded DNA and anti-Smith antibodies are highly specific for SLE but are not found in all patients. Treatment and prognosis depend on the specific manifestations of the disease, with renal and central nervous system involvement generally being the most severe manifestations and requiring aggressive therapy.