Purpose of review: The genetic basis of systemic lupus erythematosus, a complex genetic trait, may provide important insights into autoimmune disease. Innovation in both practical and theoretical approaches will assist in accelerating the pace of discovery and our understanding of pathogenesis. Recent findings: Significant progress has been made in the last year with respect to the refinement of genetic intervals to promising candidate genes involved in systemic lupus erythematosus pathogenesis and specific phenotype susceptibility. This review highlights these discoveries and suggests platforms that may affect the future of analysis of this complex disease. Summary: Understanding the genetic basis for systemic lupus erythematosus disease and sub-phenotype susceptibility will have a substantial effect on the therapeutic interventions used to care for patients. © 2005 Lippincott Williams & Wilkins.