Neurologic complications of systemic lupus erythematosus (neuro-SLE) are common. The most frequent manifestations of neuro-SLE are seizures, encephalopathy, and behavioral changes, but a wide variety of other neurologic abnormalities affecting the central and peripheral nervous system and muscle also occur. Although the prevalence of neuro-SLE is high, the diversity of clinical presentations, the multiple potential etiologies, and the absence of sensitive and specific diagnostic tests render diagnosis difficult. Recent advances in understanding mechanisms of neuronal dysfunction combined with advances in imaging techniques, including functional imaging, should help in diagnosis and management. The mechanisms of neurologic injury can be divided into three broad categories. First, neuronal dysfunction may result from direct effects of the immune system on brain cells such as autoantibody binding to cell surface, immune complex deposition with secondary inflammation, and effects of cytokines. Second, immune- mediated injury to supportive structures such as the vasculature may also affect the nervous system by producing ischemia. Finally, the neuraxis may be affected by any one of several immune and non- immune effects of infection, toxins, and metabolic disturbances.