Real or suspected brain involvement occurs in the majority of patients with systemic lupus erythematosus. The clinical manifestations are myriad and are accounted for by diverse pathogenic mechanisms. Purely psychological disturbances and psychiatric syndromes with organic components account for the majority of cases. Metabolic disturbances, drug effects, and infections may masquerade for immune-related brain dysfunction. In the absence of reliable and specific indicators of lupus brain activity, successful management requires the combined skills and clinical judgment of the rheumatologist, neurologist, and psychiatrist.