This review highlights advances made over the past 2 years in understanding the pathogenesis of systemic lupus erythematosus (lupus). The criteria used in selecting the articles include: 1) the study was performed using human subjects as opposed to animal models; 2) the quality of methods, data, and interpretation were acceptable; and 3) a current body of literature exists supporting causality for the mechanisms studied. Because lupus is a complex disorder, difficulties arise in distinguishing causal mechanisms from secondary effects. The rationale for selecting these reports rests in our present understanding of the pathogenesis of this disease. Current paradigms maintain that lupus develops in people with a genetic predisposition, but also requires an initiating event usually assumed to be environmental. Many researchers are involved in identifying genes predisposing the patient to develop lupus (1,2), and a representative article characterizing potentially pathogenic Fc receptor (Fc R) alleles is discussed. Although the initiating event for most lupus cases is unknown, studies in both human and murine systems indicate that T cells recognizing antigenic determinants in nucleosomes maintain and possibly initiate the hallmark anti-DNA antibody response (3), therefore a recent article examining this response in lupus patients is discussed. Finally, a growing body of literature indicates that the abnormal cell driving lupus is the T lymphocyte, with numerous signaling and other biochemical abnormalities reported in this profoundly disturbed cell (4). One recent paper demonstrating a signaling defect common to the majority of lupus patients is reviewed. Abnormalities in T cell DNA methylation have also been identified in lupus patients and shown to cause a lupus-like disease in animal models (5,6). Therefore a report examining the mechanisms causing DNA hypomethylation in human lupus T cells is discussed. The Fc receptor IIIA-158F allele is a major risk factor for the development of lupus nephritis among Caucasians but not non-Caucasians (Arthritis Rheum, 2001) (7)