Systemic lupus erythematosus (SLE) is an autoimmune disease whose etiology and pathogenesis are incompletely understood. Over the past 50-60 years, there has been a rise of more than ten-fold in the annual incidence of SLE in industrialized Western countries. Although it is believed that the etiology of SLE is multifactorial, including genetic, hormonal and environmental triggers, the molecular mechanisms underlying this systemic autoimmune response remain largely unknown. Clinical and epidemiological studies have revealed that SLE is rarely observed in rural tropical areas of Africa and Asia, where parasitic infections are prevalent. Indeed, tropical infections, particularly malaria, have a mysterious relation with SLE. In this review, we will focus on this relationship between infections and lupus as a prototypic autoimmune disease.