Nervous system disease in patients who have systemic lupus erythematosus (SLE) spans a wide spectrum of neurologic (N) and psychiatric (P) features that may be attributed to a primary manifestation of SLE, complications of the disease or its therapy, or a coincidental disease process. The etiology of primary NP disease is multifactorial and includes vascular injury of intracranial vessels, autoantibodies to neuronal antigens, ribosomes and phospholipid-associated proteins, and the intracranial generation of cytokines. In the absence of a diagnostic gold standard for most of the NP-SLE syndromes, a range of investigations are employed to support the clinical diagnosis and determine the severity of NP disease. Treatment remains largely empiric in the absence of controlled studies, and current strategies include the use of immunosuppressive therapies, appropriate symptomatic interventions, and the treatment of non-SLE factors.