Systemic lupus erythematosus (SLE) is the most common collagen vascular disease associated with epilepsy. Various autoantibodies have been implicated in the pathogenesis of neuropsychiatric SLE. Neuropsychiatric involvement is one of the most common clinical features of SLE, with a variable incidence reported between 15% and 75% in adults and between 20% and 85% in children. In SLE, the risk of disease is influenced by complex genetic and environmental contributions: for example, alleles including HLA-DRB1, IRF5, and STAT4 are established susceptibility genes. The diagnosis of SLE is generally a clinical one, supported by laboratory tests. With regard to neurologic involvement, radiologic techniques may be extremely helpful. In the first pediatric SLE (pSLE) study all five children who received either azathioprine or cyclophosphamide in addition to prednisone had a good recovery, while two out of 11 patients treated with prednisone alone died and three other patients had residual neurological defects.