Systemic lupus erythematosus, a complex multigenic disease, is characterized by a wide variety of clinical manifestations, as a result of the contribution of different genes or different combinations of genes. Recent advances in molecular genetics has led to a better understanding of the genes predisposing to systemic lupus erythematosus in both humans and laboratory animal models. Identification of susceptibility genes provides key insights into the pathogenesis of systemic lupus erythematosus, making new prophylactic and therapeutic approaches feasible.