Neuropsychiatric events in systemic lupus erythematosus patients may present a diagnostic and therapeutic challenge. Common and heterogeneous, their characterization and attribution to systemic lupus erythematosus and non-systemic lupus erythematosus is important and derived from clinical assessment, selection and interpretation of investigations. A standardized approach to assigning attribution has been used in recent studies. The current therapies are largely empiric, based upon known disease mechanisms and treatment of other serious organ disease in systemic lupus erythematosus. Further insight on the immunopathogenetic mechanisms and clinical outcome of neuropsychiatric systemic lupus erythematosus is required to inform the design and execution of therapeutic clinical trials.