Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that can potentially lead to serious organ complications and even death. Its global burden — in terms of incidence and prevalence, differential impact on populations, economic costs and capacity to compromise health-related quality of life — remains incompletely understood. The reported worldwide incidence and prevalence of SLE vary considerably; this variation is probably attributable to a variety of factors, including ethnic and geographic differences in the populations being studied, the definition of SLE applied, and the methods of case identification. Despite the heterogeneous nature of the disease, distinct patterns of disease presentation, severity and course can often be related to differences in ethnicity, income level, education, health insurance status, level of social support and medication compliance, as well as environmental and occupational factors. Given the potential for the disease to cause such severe and widespread organ damage, not only are the attendant direct costs high, but these costs are sometimes exceeded by indirect costs owing to loss of economic productivity. As an intangible cost, patients with SLE are, not surprisingly, likely to endure considerably reduced health-related quality of life.