Systemic lupus erythematosus (SLE) is one of the most diverse autoimmune diseases as it may affect any organ in the body and display a broad spectrum of clinical and immunological manifestations. Epidemiological studies have identified marked differences in the prevalence and course of SLE between genders, and across different ages, races and geographic locations. Methodological differences between studies may account for some of the disparity seen. Additionally, some insights into possible environmental risk factors for SLE have also been provided. As this condition is relatively uncommon, multifactorial, and largely influenced by genetic predisposition, it is inherently difficult to confirm or exclude infectious or environmental contributors to its etiology. Movement of people between communities and defining specific exposures can also be problematic. Despite these limitations, ongoing observation of SLE cohorts in multiple countries and settings, along with large international cooperative efforts in recent years, have helped clarify the risks of SLE in various groups and have defined marked differences in the worldwide occurrence of the disease.