Ethnicity is a biological and a social construct which encompasses ancestral genes, cultural, geographic and socioeconomic characteristics shared within a population. It is clear that no homogeneous racial groups exist within the human race as demonstrated when examining ancestry informative markers. Both the genetic and non-genetic components of ethnicity exert influence in the expression and outcome of systemic lupus erythematosus (SLE), including disease activity, damage accrual, work disability and mortality. Although it is difficult to determine the extent to which the differences observed in these parameters are caused by genetic or non-genetic factors, early in the disease genetic factors seem to play a more important role as determinants of the differences observed between SLE patients from various ethnic groups. Over the course of the disease, non-genetic factors seem to play a more important role. By and large, SLE is more frequent and more severe with higher disease activity and more damage accrual in non-Caucasian populations (Hispanics, African descendants and Asians) than in Caucasians. To overcome these differences it is necessary to optimize health care access to disadvantaged populations and use innovative tools to increase disease awareness and improve treatment adherence.