Ethnic variation in the frequency and outcome of systemic lupus erythematosus (SLE) has been recognized for decades. The reasons underlying these discrepancies are not completely understood but it is most likely that both genetic and nongenetic factors are responsible for them. Sorting out the extent to which these factors, particularly those of a nongenetic nature, exert their influence in SLE is not easy given inherent methodological difficulties in studying them. To establish this review properly, we would like to make it clear from the outset that ethnicity is a broad construct that implies not only biological but also nonbiological features including cultural and sociodemographic, among others. We will then describe the epidemiological differences of SLE among Caucasian and non-Caucasian populations followed by a succinct review of the genetic predisposition to SLE with special emphasis in ethnic heterogeneity. Differences in disease activity, lupus nephritis, damage and mortality as a function of ethnic group will then be described. Finally, we will present a comprehensive model of the influence of ethnicity on SLE. © 2007 Future Drugs Ltd.