Systemic lupus erythematosus (SLE) is an immunopathogenic complex disease which affect many organs of the body. Several pathogenic mechanisms have been identified. Inspite of the new knowledge about understanding the exact mechanisms and triggering parameters for SLE, the exact etiology has not been identified yet. A combination between many factors and complex reactions secondary to different genetic and environmental factors are supposed to be involved. Different genes are implicated to disease activity. Abnormal immune cascade triggered by combination of hormonal and environmental factors or some drugs or chemicals lead to abnormal immune complexes, are important contributors to the development of SLE. Certain environmental factors are supposed to be needed to trigger the disease. Activation of both B cells and T cells and other immune cells leads to activation of immune mechanism. SLE is heterogenous at presentation, that may affect one organ only or had multisystem effect, with a varying clinical presentations ranging from mild cutaneous manifestations to severe multiorgan affection or severe central nervous system affection. This makes the diagnosis and management of SLE very challenging. Management of SLE is determined according the organ involved and the severity of the disease.