A 30 year-old African-American woman with systemic lupus erythematosus (SLE) developed severe bilateral optic disc swelling followed several months later by progressive visual field loss. Neuroimaging revealed no abnormalities but a lumbar puncture revealed increased intracranial pressure (ICP), an elevated concentration of protein in the cerebrospinal fluid (CSF). Her condition did not improve despite medical therapy with leflunomide, methotrexate, prednisone, and rituximab. Consideration was given to an optic nerve sheath fenestration or a ventricular shunt procedure. She was referred to the clinic for neuro-ophthalmologic assessment and recommendations. Because of the elevated concentration of protein in her CSF, treatment was initiated with intravenous followed by oral corticosteroids. Despite this treatment, the patient’s visual fields continued to deteriorate, associated with severe, persistent bilateral disc swelling. As surgery carried a high risk of failure, more aggressive medical therapy was pursued. After rheumatologic consultation, the patient started monthly (total 6) treatments with intravenous cyclophosphamide. Her visual fields dramatically improved and the papilledema resolved. This case highlights the challenges of managing papilledema and vision loss and the potential role of cyclophosphamide in the setting of SLE-associated pseudotumor cerebri syndrome.