Systemic lupus erythematosus (SLE) is known to occur in all populations across the globe. In many respects SLE is similar across regions in its spectrum of clinical features, but the severity of the disease and comorbidity are appreciably different in the developing and industrialized worlds. Although data on the prevalence of SLE among Africans and Asians living in the tropics are limited, SLE is reportedly more common and more severe in people of African and Asian extraction living in industrialized countries. Renal disease is especially common in SLE patients in the developing world and is a major cause of morbidity and mortality. Discoid lupus and lymphopenia are frequent clinical features of SLE in patients of African extraction. Thrombotic complications and associated anti-phospholipid antibodies are less common in the Chinese and Black African SLE patients than in Caucasian patients. High frequencies of antibodies to extractable nuclear antigens, especially anti-Sm and anti-U1RNP, have been reported in SLE patients in many developing countries. Infections, including tuberculosis, are among the most important causes of comorbidity and mortality in SLE across all regions of the developing world. With a few exceptions, survival rates for SLE patients in developing countries are substantially lower than those reported in industrialized countries, with early death from infection and active disease. The bimodal pattern of mortality observed in many industrialized countries, is also less evident. While the poorer outcome in developing countries is partly related to inherent genetic differences, better outcomes can be achieved if new initiatives are undertaken to define the burden of disease, increase public awareness, and establish algorithms for diagnosis and treatment based on the available resources and local health-care delivery systems.